42 results on '"Paul Salm"'
Search Results
2. Cloned Enzyme Donor Immunoassay Tacrolimus Assay Compared With High-Performance Liquid Chromatography-Tandem Mass Spectrometry and Microparticle Enzyme Immunoassay in Liver and Renal Transplant Recipients
- Author
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Ian S. Westley, Raymond G. Morris, Paul Salm, and Paul J. Taylor
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Urology ,Microparticle Enzyme Immunoassay ,Liver transplantation ,High-performance liquid chromatography ,Mass Spectrometry ,Tacrolimus ,Immunoenzyme Techniques ,medicine ,Humans ,Pharmacology (medical) ,Child ,Chromatography, High Pressure Liquid ,Kidney transplantation ,Aged ,Pharmacology ,Chromatography ,medicine.diagnostic_test ,Chemistry ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Kidney Transplantation ,Clone Cells ,Liver Transplantation ,Transplantation ,surgical procedures, operative ,Therapeutic drug monitoring ,Immunoassay ,Female ,Drug Monitoring ,Immunosuppressive Agents - Abstract
The immunosuppressant drug tacrolimus has a narrow therapeutic index and is subject to a large variation in individual bioavailability and clearance. With its narrow therapeutic index, therapeutic drug monitoring is standard clinical practice in the management of transplant recipients. In this study, we report the evaluation of the cloned enzyme donor immunoassay (CEDIA) for the determination of whole-blood tacrolimus concentrations compared with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and microparticle enzyme immunoassay (MEIA) using samples obtained from liver (n = 100) and renal (n = 88) transplant recipients. Linear regression analysis showed a relationship of CEDIA = 1.24 HPLC-MS/MS -0.18 (r = 0.81). The mean bias (+/-SEM) for all patients when compared with HPLC-MS/MS was 22.2% (+/-2.1%). The precision of the CEDIA method for all samples showed a root mean square error of 3.1 microg/L. Liver transplant recipient samples showed a mean (+/-SEM) bias compared with HPLC-MS/MS of 12.5% (+/-1.6%). The precision of the CEDIA method for these samples showed a root mean square error of 1.5 microg/L. The data suggest that in the renal transplant group, the CEDIA and MEIA methods have a bias of 33.3% and 20.1%, respectively, compared with HPLC-MS/MS. The CEDIA tacrolimus immunoassay has been shown to be a rapid method for the determination of whole-blood tacrolimus concentrations and may be considered when HPLC-MS/MS is not available. When used in the clinical setting with other parameters, it would be a useful adjunct in the management of liver transplant recipients, but a significant bias in renal transplant patients needs to be further investigated.
- Published
- 2007
3. FTY720, a Synthetic Sphingosine 1 Phosphate Analogue, Inhibits Development of Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice
- Author
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Volker Brinkmann, Martin Brodde, Erik A.L. Biessen, Gerd Assmann, Paul J. Taylor, Martine Bot, Paul Salm, Theo van Berkel, and Jerzy-Roch Nofer
- Subjects
medicine.medical_specialty ,Ratón ,Inflammation ,Mice ,chemistry.chemical_compound ,Sphingosine ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Lymphocyte Count ,Lymphocytes ,Sphingosine-1-phosphate ,Triglycerides ,Fingolimod Hydrochloride ,Vascular disease ,business.industry ,Macrophages ,Cholesterol, HDL ,Atherosclerosis ,medicine.disease ,Mice, Mutant Strains ,In vitro ,Mice, Inbred C57BL ,Disease Models, Animal ,Endocrinology ,Receptors, LDL ,chemistry ,Propylene Glycols ,LDL receptor ,Immunology ,Cytokines ,Female ,Lysophospholipids ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Cell Division ,Immunosuppressive Agents ,Signal Transduction ,Lipoprotein - Abstract
Background— Numerous in vitro studies suggest that sphingosine 1-phosphate (S1P), a bioactive lysosphingolipid associated with high-density lipoproteins, accounts at least partly for the potent antiinflammatory properties of high-density lipoprotein and, thereby, contributes to the antiatherogenic potential attributed to high-density lipoproteins. The present study was undertaken to investigate whether modulation of S1P signaling would affect atherosclerosis in a murine model of disease. Methods and Results— Low-density lipoprotein receptor–deficient mice on a cholesterol-rich diet were given FTY720, a synthetic S1P analogue, at low (0.04 mg/kg per day) or high (0.4 mg/kg per day) doses for 16 weeks. FTY720 dose-dependently reduced atherosclerotic lesion formation, both in the aortic root and brachiocephalic artery, and almost completely blunted necrotic core formation. Plasma lipids remained unchanged during the course of FTY720 treatment. However, FTY720 lowered blood lymphocyte count (at a high dose) and significantly interfered with lymphocyte function, as evidenced by reduced splenocyte proliferation and interferon-γ levels in plasma. Plasma concentrations of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-6, IL-12, and regulated on activation normal T cell expressed and secreted were reduced by FTY720 administration. Moreover, lipopolysaccharide-elicited generation of nitrite/nitrate and IL-6—two markers of classical (M1) macrophage activation—was inhibited, whereas IL-4–induced production of IL-1–receptor antagonist, a marker of alternative (M2) macrophage activation, was augmented in peritoneal macrophages from FTY720-treated low-density lipoprotein receptor–deficient mice. Conclusions— The present results demonstrate that an S1P analogue inhibits atherosclerosis by modulating lymphocyte and macrophage function, and these results are consistent with the notion that S1P contributes to the antiatherogenic potential of high-density lipoprotein.
- Published
- 2007
4. Measurement and stability of FTY720 in human whole blood by high-performance liquid chromatography–atmospheric pressure chemical ionization–tandem mass spectrometry
- Author
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Paul Salm, Paul J. Taylor, Christopher Warnholtz, and Stephen V. Lynch
- Subjects
Chromatography ,Fingolimod Hydrochloride ,Chemistry ,Electrospray ionization ,Clinical Biochemistry ,Selected reaction monitoring ,Analytical chemistry ,Atmospheric-pressure chemical ionization ,Cell Biology ,General Medicine ,Tandem mass spectrometry ,Mass spectrometry ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,Drug Stability ,Propylene Glycols ,Sphingosine ,Tandem Mass Spectrometry ,Ionization ,Humans ,Quantitative analysis (chemistry) ,Chromatography, High Pressure Liquid - Abstract
We report here a validated method for the quantification of a new immunosuppressant drug FTY720, using HPLC-tandem mass spectrometry. Whole blood samples (500 microl) were subjected to liquid-liquid extraction, in the presence of an internal standard (Y-32919). Mass spectrometric detection was by selected reaction monitoring with an atmospheric pressure chemical ionization source in positive ionization mode (FTY720: m/z 308.3-->255.3). The assay was linear from 0.2 to 25 microg/l (r(2)>0.997, n=5). The inter- and intra-day analytical recovery and imprecision for quality control samples (0.5, 7 and 15 microg/l) were 95.8-103.2 and
- Published
- 2006
5. Comparison of the Reintroduced MEIA® Assay With HPLC-MS/MS for the Determination of Whole-Blood Sirolimus From Transplant Recipients
- Author
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Anastasia Theodossi, Paul J. Taylor, Fiona A Wicks, Paul Salm, and Raymond G. Morris
- Subjects
medicine.medical_specialty ,Urology ,Microparticle Enzyme Immunoassay ,Hematocrit ,Mass Spectrometry ,Immunoenzyme Techniques ,Deming regression ,Monitoring, Immunologic ,medicine ,Humans ,Pharmacology (medical) ,Particle Size ,Chromatography, High Pressure Liquid ,Whole blood ,Sirolimus ,Pharmacology ,Chromatography ,Dose-Response Relationship, Drug ,medicine.diagnostic_test ,Chemistry ,Reproducibility of Results ,Kidney Transplantation ,Transplantation ,Therapeutic drug monitoring ,Immunoassay ,Immunosuppressive Agents ,medicine.drug - Abstract
Therapeutic monitoring with dosage individualization of sirolimus drug therapy is standard clinical practice for organ transplant recipients. For several years sirolimus monitoring has been restricted as a result of lack of an immunoassay. The recent reintroduction of the microparticle enzyme immunoassay (MEIA (R)) for sirolimus on the IMx (R) analyser has the potential to address this situation. This Study, using patient samples, has compared the MEIA (R) sirolimus method with an established HPLC-tandem mass spectrometry method (HPLC-MS/MS). An established HPLC-UV assay was used for independent cross-validation. For quality control materials (5, 11, 22 mu g/L), the MEIA (R) showed acceptable validation criteria based on intra-and inter-run precision (CV) and accuracy (bias) of < 8% and < 13%, respectively. The lower limit of quantitation was found to be approximately 3 mu g/L. The performance of the immunoassay was compared with HPLC-MS/MS using EDTA whole-blood samples obtained from various types of organ transplant recipients (n = 116). The resultant Deming regression line was: MEIA = 1.3 x HPLC-MS/MS+ 1.3 (r = 0.967, s(y/x) = 1) with a mean bias of 49.2% +/- 23.1 % (range, -2.4% to 128%; P < 0.001). The reason for the large and variable bias was not explored in this study, but the sirolimus-metabolite cross-reactivity with the MEIA (R) antibody could be a substantive contributing factor. Whereas the MEIA (R) sirolimus method may be an adjunct to sirolimus dosage individualization in transplant recipients, users must consider the implications of the substantial and variable bias when interpreting results. In selected patients where difficult clinical issues arise, reference to a specific chromatographic method may be required.
- Published
- 2006
6. A Detection Scheme for Paraquat Poisoning: Validation and a Five-Year Experience in Australia
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Paul J. Taylor, Paul Salm, and Peter I. Pillans
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Paraquat ,Detection limit ,Chemical Health and Safety ,Chromatography ,Herbicides ,Chemistry ,Poisoning ,Health, Toxicology and Mutagenesis ,Urine ,Toxicology ,Sensitivity and Specificity ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,Linear range ,Reference Values ,Calibration ,Humans ,Environmental Chemistry ,False Positive Reactions ,Sample preparation ,Solid phase extraction ,Quantitative analysis (chemistry) ,Chromatography, High Pressure Liquid - Abstract
We report the validation of a quantitative method for paraquat in plasma and urine using high-performance liquid chromatography (HPLC) with ultraviolet detection (260 nm). Furthermore, we illustrate the use of this method in the clinic (over five years), in conjunction with a qualitative urine paraquat screen. Urine or plasma sample (1 mL) preparation was performed in duplicate using C18 solid-phase extraction. Chromatographic separation was achieved on a Zorbax RX-Silica column (250 x 4.6-mm i.d.). The mobile phase consisted of 96% sodium chloride (5 g/L) and 4% acetonitrile (pH 2.2) pumped at 1.0 mL/min. Using a single-point calibration (1.0 mg/L), the method was found to be linear from 0.1 to 5.0 mg/L. The accuracy and imprecision of the method, over the linear range and for plasma and urine, were 94.7-104.9% and12.2%, respectively. The limit of quantitation for both matrices was 0.1 mg/L. The absolute recovery of paraquat from plasma and urine was 79.9 +/- 5.3% and 88.2 +/- 5.3%, respectively. From January 1995 to February 2000, 47 qualitative urine paraquat screens were requested throughout Australia. Nine screens were positive, and eight were confirmed to have paraquat present by our HPLC method. One sample was not analyzed by HPLC because the patient died prior to analysis. Thus, no false-positive results were reported for the qualitative urine screen. An additional 11 samples were referred for patients with positive screens from other sites for HPLC confirmation. The presence of paraquat was confirmed in nine of these samples. In conclusion, a qualitative urine screen combined with our validated HPLC confirmation is an effective protocol for assessing suspected cases of paraquat poisoning.
- Published
- 2001
7. Stability of Sirolimus (Rapamycin) in Whole Blood
- Author
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Peter I. Pillans, Paul J. Taylor, Paul Salm, and Michael J. Tresillian
- Subjects
Sirolimus ,Pharmacology ,medicine.medical_specialty ,medicine.diagnostic_test ,Chemistry ,Urology ,equipment and supplies ,surgical procedures, operative ,Drug Stability ,Therapeutic drug monitoring ,cardiovascular system ,medicine ,Humans ,Pharmacology (medical) ,cardiovascular diseases ,Immunosuppressive Agents ,medicine.drug ,Whole blood - Abstract
The effects of storage time (0-8 days), temperature (4 degrees C and 30 degrees C in dark and light), and freeze-thaw cycles on the stability of sirolimus in blood were examined. Sirolimus quantification was undertaken using HPLC-electrospray-tandem mass spectrometry. Whole blood samples supplemented with sirolimus (5.0, 15.0, and 30.0 microg/L) and pooled renal and heart transplant samples were found to be stable during the 8 days under all conditions (10% decrease in concentration). No significant difference was observed in sirolimus concentration between freshly collected patient samples and sirolimus-supplemented samples (5.0, 15.0, and 30.0 microg/L) after three freeze-thaw cycles (p0.198). In conclusion, blood samples can be transported with or without cooling for up to 8 days without sirolimus results being compromised. The reanalysis of sirolimus samples, which may entail freeze-thaw cycles, can be undertaken if the number of cycles is three or less.
- Published
- 2000
8. The quantification of sirolimus by high-performance liquid chromatography-tandem mass spectrometry and microparticle enzyme immunoassay in renal transplant recipients
- Author
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Peter I. Pillans, Paul J. Taylor, and Paul Salm
- Subjects
Quality Control ,medicine.medical_specialty ,Urology ,Microparticle Enzyme Immunoassay ,Pharmacology ,Tandem mass spectrometry ,High-performance liquid chromatography ,Mass Spectrometry ,Cohort Studies ,Immunoenzyme Techniques ,Double-Blind Method ,medicine ,Humans ,Pharmacology (medical) ,cardiovascular diseases ,Chromatography, High Pressure Liquid ,Sirolimus ,Autoanalysis ,medicine.diagnostic_test ,business.industry ,Reproducibility of Results ,equipment and supplies ,Kidney Transplantation ,Transplantation ,surgical procedures, operative ,Therapeutic drug monitoring ,Renal transplant ,Hemoglobin ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Sirolimus, an immunosuppressive agent, is undergoing clinical trials in the prophylaxis of organ rejection.The aim of this study was to compare the performance of the semi-automated prototype (mode IA) microparticle enzyme immunoassay (MEIA) against a validated high-performance liquid chromatography-mass spectrometry (HPLC-MS) method for measuring sirolimus concentrations. A secondary objective was to identify potential factors that may influence sirolimus measurement.The comparison was based on predose samples (n = 841) from 74 renal transplant patients receiving sirolimus therapy. Samples were collected up to 12 months after transplantation.The mean (+/- SD) overestimation by MEIA was 42.5%+/-16.9%. Several variables were investigated to determine potential contributors to the observed overestimation. Stratification of the data based on the mean sirolimus concentrations determined by both assays yielded no statistically significant differences in bias between concentration subgroups within the clinically relevant range. Multiple linear regression analysis identified HPLC-MS sirolimus concentration (P = 0.03), hemoglobin concentration (P0.001), and time after transplantation (P0.001) as significant variables in the prediction of overestimation by MEIA. Analysis of the effect of time after transplantation on overestimation yielded a statistically significant difference up to 6 months after transplantation (35.6% to 46.4%) compared with 9 (23.9%) and 12 months (24.4%). A relationship between hemoglobin concentration and time after transplantation may explain the reduction in bias observed after 6 months.The MEIA overestimates sirolimus concentrations in renal transplant patients compared with HPLC-MS. The clinical importance of this observed overestimation requires further investigation.
- Published
- 2000
9. High-Performance Liquid Chromatography-Tandem Mass Spectrometry as a Reference for Analysis of Tacrolimus to Assess Two Immunoassays in Patients With Liver and Renal Transplants
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Glenda A. Balderson, Paul Salm, Susan M. Pond, Leslie M. Shaw, Anthony Grygotis, Paul J. Taylor, Stephen V. Lynch, Ross Norris, and Andrea Clark
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Enzyme-Linked Immunosorbent Assay ,Microparticle Enzyme Immunoassay ,Tandem mass spectrometry ,High-performance liquid chromatography ,Mass Spectrometry ,Tacrolimus ,Therapeutic index ,Reference Values ,medicine ,Humans ,Pharmacology (medical) ,Chromatography, High Pressure Liquid ,Immunoassay ,Pharmacology ,Detection limit ,Chromatography ,medicine.diagnostic_test ,Chemistry ,Kidney Transplantation ,Liver Transplantation ,Therapeutic drug monitoring ,Immunology ,Drug Monitoring ,Quantitative analysis (chemistry) ,Immunosuppressive Agents - Abstract
The accuracy and imprecision of three assays used for therapeutic monitoring of tacrolimus were tested using blood-containing weighed-in amounts of the drug, an enzyme-linked immunosorbent assay (ELISA), a microparticle enzyme immunoassay (MEIA I), and a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS2) assay. Accuracy was acceptable for the HPLC-MS2 assay at all concentrations tested (10% deviation) and for the ELISA at 1.0 and 4.0 microg/l. Accuracy was not acceptable for the ELISA at 15.0 and 50.0 microg/l or for the MEIA I at all concentrations tested. Imprecision was acceptable for the HPLC-MS2 assay at all concentrations tested (coefficient of variation10%), for the ELISA at 15.0 and 50.0 microg/l, and for the MEIA I at 15.0 and 50.0 microg/l. Imprecision was not acceptable for the ELISA at 1.0 and 4.0 microg/l or for the MEIA I at 1.0 and 4.0 microg/l. This assessment with weighed-in amounts of tacrolimus verified the HPLC-MS2 assay as a reference method. The performance of the two immunoassays with HPLC-MS2 was then compared in the clinical setting using blood from patients with liver (n = 30) and renal (n = 37) transplants. In the liver transplant group (127 samples), the range of tacrolimus concentrations measured by HPLC-MS2, ELISA, and MEIA I was 1.9 to 31.8, 2.1 to 35.0, and less than 0.1 to 36.5 mg/l, respectively. In the renal transplant group (129 samples), the ranges were 1.7 to 26.1, 1.9 to 24.4, and 0.9 to 28.5 microg/l, respectively. Compared with the HPLC-MS2, the ELISA had minimal bias (0.1 to 0.2 microg/l) but unacceptable variability in values (SD13%). The MEIA I had unacceptable bias (1.7-1.8 microg/l) and variability (SD23%). These data indicated that neither the ELISA nor MEIA I is interchangeable with HPLC-MS2. Moreover, in view of the current trend to reduce the therapeutic dose of tacrolimus, quantitative results using the MEIA I would not be obtainable during therapeutic drug monitoring in some patients in whom effective therapeutic concentrations can be less than 5.0 microg/l.
- Published
- 1997
10. Comparison of High-Performance Liquid Chromatography and Monoclonal Fluorescence Polarization Immunoassay for the Determination of Whole-Blood Cyclosporin A in Liver and Heart Transplant Patients
- Author
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Peter J. Ravenscroft, Ross Norris, Paul Salm, Paul J. Taylor, and Susan M. Pond
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Pharmacology ,Chromatography ,Heart disease ,Chemistry ,Antibodies, Monoclonal ,medicine.disease ,High-performance liquid chromatography ,Liver Transplantation ,Transplantation ,Cyclosporin a ,Calibration ,Fluorescence Polarization Immunoassay ,Monoclonal ,Cyclosporine ,medicine ,Fluorescence polarization immunoassay ,Heart Transplantation ,Humans ,Pharmacology (medical) ,Reagent Kits, Diagnostic ,Quantitative analysis (chemistry) ,Chromatography, High Pressure Liquid ,Whole blood - Abstract
Conflicting conclusions have been drawn from comparisons of high-performance liquid chromatography (HPLC) and the Abbott Diagnostics monoclonal fluorescence polarization immunoassay (mFPIA) for cyclosporin. The aim of this study was to compare whole blood cyclosporin A (CsA) concentrations measured by both mFPIA and HPLC in liver and heart transplant patients. One hundred and twenty-four liver and 62 heart transplant patient samples were assayed by both methods. Assay imprecision for both methods during the studies was < 7% over the range 150-800 micrograms/L. At an HPLC-determined concentration of 100 micrograms/L, mFPIA overestimated CsA by 60% (liver) and 77% (heart). At 300 micrograms/L, the overestimation was 40% (liver) and 45% (heart). On this basis, the mFPIA is not interchangeable with HPLC.
- Published
- 1994
11. Rapid rise in serum theophylline concentration after overdose with sustained release theophylline
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Alan Henderson, Paul Salm, and Susan M Pond
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Rapid rise ,business.industry ,Medicine ,Theophylline ,General Medicine ,Pharmacology ,business ,medicine.drug - Published
- 1992
12. Mechanisms of scaling up: combining a realist perspective and systems analysis to understand successfully scaled interventions
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Harriet Koorts, Samuel Cassar, Jo Salmon, Mark Lawrence, Paul Salmon, and Henry Dorling
- Subjects
Scale up ,Systems ,Physical activity ,Nutrition ,Intervention ,Realist evaluation ,Nutritional diseases. Deficiency diseases ,RC620-627 ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Sustainable shifts in population behaviours require system-level implementation and embeddedness of large-scale health interventions. This paper aims to understand how different contexts of scaling up interventions affect mechanisms to produce intended and unintended scale up outcomes. Methods A mixed method study combining a realist perspective and systems analysis (causal loop diagrams) of scaled-up physical activity and/or nutrition interventions implemented at a state/national level in Australia (2010–18). The study involved four distinct phases: Phase 1 expert consultation, database and grey literature searches to identify scaled-up interventions; Phase 2 generating initial Context-Mechanism-Outcome configurations (CMOs) from the WHO ExpandNet framework for scaling up; Phase 3 testing and refining CMOs via online surveys and realist interviews with academics, government and non-government organisations (NGOs) involved in scale up of selected interventions (Phase 1); and Phase 4 generating cross-case mid-range theories represented in systems models of scaling up; validated by member checking. Descriptive statistics were reported for online survey data and realist analysis for interview data. Results Seven interventions were analysed, targeting nutrition (n = 1), physical activity (n = 1), or a combination (n = 5). Twenty-six participants completed surveys; 19 completed interviews. Sixty-three CMO pathways underpinned successful scale up, reflecting 36 scale up contexts, 8 key outcomes; linked via 53 commonly occurring mechanisms. All five WHO framework domains were represented in the systems models. Most CMO pathways included ‘intervention attributes’ and led to outcomes ‘community sustainability/embeddedness’ and ‘stakeholder buy-in/perceived value’. Irrespective of interventions being scaled in similar contexts (e.g., having political favourability); mechanisms still led to both intended and unintended scale up outcomes (e.g., increased or reduced sustainability). Conclusion This paper provides the first evidence for mechanisms underpinning outcomes required for successful scale up of state or nationally delivered interventions. Our findings challenge current prerequisites for effective scaling suggesting other conditions may be necessary. Future scale up approaches that plan for complexity and encourage iterative adaptation throughout, may enhance scale up outcomes. Current linear, context-to-outcome depictions of scale up oversimplify what is a clearly a complex interaction between perceptions, worldviews and goals of those involved. Mechanisms identified in this study could potentially be leveraged during future scale up efforts, to positively influence intervention scalability and sustainability.
- Published
- 2021
- Full Text
- View/download PDF
13. Analytical Performance of Microparticle Enzyme Immunoassay and HPLC-Tandem Mass Spectrometry in the Determination of Sirolimus in Whole Blood
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Peter I. Pillans, Paul J. Taylor, and Paul Salm
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Chromatography ,medicine.diagnostic_test ,Chemistry ,Biochemistry (medical) ,Clinical Biochemistry ,Microparticle Enzyme Immunoassay ,Tandem mass spectrometry ,High-performance liquid chromatography ,Transplantation ,Therapeutic drug monitoring ,medicine ,Trough Concentration ,Quantitative analysis (chemistry) ,Whole blood - Abstract
The potent immunosuppressant agent sirolimus (rapamycin; Wyeth-Ayerst) is undergoing clinical trials in solid-organ transplantation (1)(2). Evidence suggests that therapeutic drug monitoring of trough sirolimus concentrations may be beneficial for two fundamental reasons: (a) a strong correlation between the trough concentration and the area under the concentration-time curve has been shown; and (b) a strong correlation between the evidence of toxicity and trough concentrations substantially >15 μg/L has been reported (3). To date, there have been only HPLC methods available to measure sirolimus in human whole blood. These include HPLC with mass spectrometric detection (4)(5) and HPLC with ultraviolet detection (6)(7)(8)(9). As an alternative, a semiautomated method utilizing the IMx analyzer (Abbott Diagnostics) that incorporates microparticle enzyme immunoassay (MEIA) technology has been developed. There are two versions of the MEIA for sirolimus in whole blood, the prototype version (Mode 1A) and the recently manufactured premarket version (Mode 1C). Both of these assays are undergoing evaluation based on their analytical performance and clinical use. This study compares the analytical performance of the prototype MEIA (Mode 1A) with HPLC-tandem mass spectrometry (HPLC-MS) within one center through evaluation of interference with endogenous and exogenous compounds, imprecision, recovery, and the quantification range. In addition, blood samples from renal transplant patients receiving sirolimus therapy are compared using both methods. Throughout this study, HPLC-MS was performed as per our reported method (4) and MEIA according to manufacturer’s instructions. All patient specimens were stored at −75 °C until analysis. Investigation into potential interferences in HPLC-MS and MEIA in relation to endogenous compounds was determined based on 209 samples collected into EDTA tubes from 23 renal transplant recipients …
- Published
- 1999
14. Liquid chromatography-tandem mass spectrometry method for the simultaneous quantitative determination of the organophosphorus pesticides dimethoate, fenthion, diazinon and chlorpyrifos in human blood
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Darren M. Roberts, Janaka de Silva, Paul J. Taylor, and Paul Salm
- Subjects
Adult ,Diazinon ,Clinical Biochemistry ,Mass spectrometry ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,chemistry.chemical_compound ,Liquid chromatography–mass spectrometry ,Tandem Mass Spectrometry ,Protein precipitation ,Humans ,Dimethoate ,Pesticides ,Fenthion ,Chromatography ,Pesticide residue ,Chemistry ,Reproducibility of Results ,Cell Biology ,General Medicine ,Reference Standards ,Female ,Chlorpyrifos ,Chromatography, Liquid - Abstract
Simultaneous determination of the organophosphorus pesticides dimethoate, fenthion, diazinon and chlorpyrifos in human blood by HPLC-tandem mass spectrometry was developed and validated. The pesticides were extracted by a simple one-step protein precipitation procedure. Chromatography was performed on a Luna C(18) (30mmx2.0mm, 3microm) column, using a step-gradient at a flow rate of 0.4ml/min. The assay was linear from 0.5 to 100ng/ml (r(2)0.992, n=24) for all pesticides. The inter- and intra-day accuracy and precision for the method was 96.6-106.1% and10%, respectively. The lower limit of quantification was 0.5ng/ml. In conclusion, the method described displays analytical performance characteristics that are suitable for the quantification of these pesticides in cases of acute poisoning.
- Published
- 2008
15. A high-performance liquid chromatography-mass spectrometry method using a novel atmospheric pressure chemical ionization approach for the rapid simultaneous measurement of tacrolimus and cyclosporin in whole blood
- Author
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Frank Rooney, Paul Salm, and Paul J. Taylor
- Subjects
Pharmacology ,Quality Control ,Chromatography ,Chemistry ,Coefficient of variation ,Selected reaction monitoring ,Analytical chemistry ,Reproducibility of Results ,Atmospheric-pressure chemical ionization ,Reference Standards ,Mass spectrometry ,High-performance liquid chromatography ,Mass Spectrometry ,Tacrolimus ,Transplantation ,Liquid chromatography–mass spectrometry ,medicine ,Cyclosporine ,Humans ,Pharmacology (medical) ,Ascomycin ,Chromatography, High Pressure Liquid ,Immunosuppressive Agents ,medicine.drug - Abstract
Concentration monitoring and dose individualization is required to optimize either tacrolimus or cyclosporin therapy. In this study, the validation of a simple, rapid high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous measurement of tacrolimus and cyclosporin in whole blood is reported. Blood samples (100 microL) were prepared by protein precipitation with zinc sulphate followed by acetonitrile (containing the internal standards ascomycin and cyclosporin D). The chromatographic run time was 1.5 minutes per sample. Mass spectrometric detection was by selected reaction monitoring with an atmospheric pressure chemical ionization source in negative ionization mode (tacrolimus: m/z 802.5 --> 560.6, cyclosporin: m/z 1200.8 --> 1088.4). The assay had an analytical range of 1.0 to 30 mug/L (r > 0.998, n = 6) for tacrolimus and 25 to 2000 microg/L (r > 0.999, n = 6) for cyclosporin. Tacrolimus inter- and intraday inaccuracy and precision [coefficient of variation (CV)] using quality control samples (2.5, 12.5, 25 microg/L) was less than +/-10.0% and CV less than 5.0%, respectively (n = 5). Similarly, cyclosporin inter- and intraday inaccuracy and precision using quality control samples (70, 400, 1500 microg/L) was less than +/-2.0% and CV less than 5.0%, respectively (n = 5). The lower limit of quantification for tacrolimus was 1.0 mug/L and cyclosporin 25 microg/L. The assay had an absolute mean recovery of 86.7% for tacrolimus and 89.0% for cyclosporin (n = 15). Intersubject variability, as a measure of potential matrix effects on results, was less than 6.0% CV for both analytes (n = 15). Extracted samples were stable for at least 20 hours. Results obtained from external proficiency testing samples measured by this method compared with the mean of all liquid chromatography-tandem mass spectrometry methods used by scheme participants revealed a strong correlation and good agreement for tacrolimus (r = 0.993, mean bias = -10.3%, n = 19) and cyclosporin (r = 0.996, mean bias = 3.0%, n = 20). In conclusion, this is the first reported high-throughput method that uses negative atmospheric pressure chemical ionization for the simultaneous measurement of tacrolimus and cyclosporin in whole blood.
- Published
- 2008
16. Eight human factors and ergonomics principles for healthcare artificial intelligence
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Mark Sujan, Rachel Pool, and Paul Salmon
- Subjects
Computer applications to medicine. Medical informatics ,R858-859.7 - Published
- 2022
- Full Text
- View/download PDF
17. Evaluation of a fluorescent polarization immunoassay for whole blood everolimus determination using samples from renal transplant recipients
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Peter Marbach, Jared Boyd, Paul Salm, Paul J. Taylor, Christopher Warnholtz, and Lili Arabshahi
- Subjects
medicine.medical_specialty ,Fluorescent polarization ,Clinical Biochemistry ,Urology ,Cross Reactions ,Deming regression ,Fluorescence Polarization Immunoassay ,medicine ,Humans ,Everolimus ,Longitudinal Studies ,Kidney transplantation ,Chromatography, High Pressure Liquid ,Whole blood ,Sirolimus ,Chromatography ,medicine.diagnostic_test ,Chemistry ,General Medicine ,medicine.disease ,Kidney Transplantation ,Therapeutic drug monitoring ,Immunoassay ,Immunosuppressive Agents ,medicine.drug - Abstract
Objectives: This study compared the performance of a fluorescent polarization immunoassay (FPIA) against HPLC-tandem mass spectrometry (HPLC-MS) for the measurement of everolimus in renal transplant recipients. Design and methods: A total of 333 pre-dose samples from 45 renal transplant patients were analyzed by FPIA and HPLC-MS. Results: The inter-batch inaccuracy and precision of the FPIA for control samples were ≤6% and ≤13.0%, respectively ( n = 17). The comparison of patient results yielded the Deming regression equation FPIA = 1.19 × HPLC-MS + 0.51. The mean bias was 24.4% (95% CI: −3.0 to 54.2%, range: −30.1% to 79.4%). Conclusions: The FPIA had acceptable analytical performance during the study but compared to HPLC-MS overestimated everolimus in patient samples. This overestimation is probably due to calibration differences between the methods and cross-reactivity of the FPIA antibody with everolimus metabolites. The clinical importance of the observed overestimation by FPIA requires further investigation.
- Published
- 2005
18. Evaluation of 3 internal standards for the measurement of cyclosporin by HPLC-mass spectrometry
- Author
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Stephen V. Lynch, Donald P. Cooper, Michael Morris, Scott R Brown, Paul J. Taylor, Peter I. Pillans, and Paul Salm
- Subjects
Chromatography ,Chemistry ,Biochemistry (medical) ,Clinical Biochemistry ,High-performance liquid chromatography ,Mass Spectrometry ,Calcineurin ,Therapeutic index ,Pharmacokinetics ,Cyclosporin a ,medicine ,Cyclosporine ,Humans ,Ascomycin ,Quantitative analysis (chemistry) ,Chromatography, High Pressure Liquid ,medicine.drug ,Whole blood - Abstract
The calcineurin inhibitor cyclosporin A (CsA) is used as a primary immunosuppressant in solid organ transplantation and for the treatment of many autoimmune diseases. Individualization of therapy is required because CsA has high inter- and intrapatient pharmacokinetic variability, the potential for drug interactions, a narrow therapeutic index, and important compliance issues (1). The use of the CsA formulation Neoral® has been associated with a shift in monitoring from trough (predose) to 2-h postdose (C2) whole blood samples (2)(3). To provide efficient CsA therapeutic drug-monitoring, a rapid turnaround of results, high selectivity, and high sensitivity are required (4). These requirements have led to the development of several high-throughput HPLC–mass spectrometry (HPLC-MS) methods (4)(5)(6)(7)(8)(9). For quantification purposes, internal standardization is used in all methods. Currently, there is no consensus on the preferred internal standard for CsA measurement. To date, the internal standards that have been used can be classified into 3 types: isotope-labeled CsA (10)(11), a structural analog (8)(12), or a structurally unrelated compound (4)(5). The aim of this study was to evaluate the analytical performance of these 3 classes of internal standards with deuterium-labeled CsA (CsA-d12), cyclosporin D (CsD), and ascomycin for the quantification of CsA by a high-throughput HPLC-MS method. The HPLC-MS method in this study is a modification based on the previously reported assay by Keevil et al. (5). Whole blood samples (50 μL) were treated with 0.1 mol/L zinc sulfate (200 μL) followed by acetonitrile (500 μL) containing internal standard (50 μg/L). Because of interference from CsA-d12 in the CsD mass transition, 2 extractions were performed and analyzed: 1 with …
- Published
- 2005
19. CEDIA sirolimus assay compared with HPLC-MS/MS and HPLC-UV in transplant recipient specimens
- Author
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Ian S. Westley, Paul Salm, Maree J James, Paul J. Taylor, and Raymond G. Morris
- Subjects
Pharmacology ,Sirolimus ,Chromatography ,medicine.diagnostic_test ,business.industry ,Ultraviolet Rays ,Transplant recipient ,Cross Reactions ,Kidney Transplantation ,Lower limit ,Mass Spectrometry ,Deming regression ,Hplc ms ms ,Renal transplant ,Therapeutic drug monitoring ,Immunoassay ,medicine ,Humans ,Pharmacology (medical) ,business ,Chromatography, High Pressure Liquid ,Immunosuppressive Agents ,medicine.drug - Abstract
The role of the therapeutic drug monitoring laboratory in support of immunosuppressant drug therapy is well established, and the introduction of sirolimus (SRL) is a new direction in this field. The lack of an immunoassay for several years has restricted the availability of SRL assay services. The recent availability of a CEDIA (R) SRL assay has the potential to improve this situation. The present communication has compared the CEDIA (R) SRL method with 2 established chromatographic methods, HPLC-UV and HPLC-MS/MS. The CEDIA (R) method, run on a Hitachi 917 analyzer, showed acceptable validation criteria with within-assay precision of 9.1% and 3.3%, and bias of 17.1% and 5.8%, at SRL concentrations of 5.0 mu g/L and 20 mu g/L, respectively. The corresponding between-run precision values were 11.5% and 3.3% and bias of 7.1% and 2.9% at 5.0 mu g/L and 20 mu g/L, respectively, The lower limit of quantification was found to be 3.0 mu g/L. A series of 96 EDTA whole-blood samples predominantly from renal transplant recipients were assayed by the 3 methods for comparison. It was found that the CEDIA (R) method showed a Deming regression line of CEDIA = 1.20 X HPLC-MS/MS - 0.07 (r = 0.934, SEE = 1.47), with a mean bias of 20.4%. Serial blood samples from 8 patients included in this evaluation showed that the CEDIA (R) method reflected the clinical fluctuations in the chromatographic methods, albeit with the variable bias noted. The CEDIA (R) method on the H917 analyzer is therefore a useful adjunct to SRL dosage individualization in renal transplant recipients.
- Published
- 2005
20. A rapid HPLC-mass spectrometry cyclosporin method suitable for current monitoring practices
- Author
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Peter I. Pillans, Christopher Warnholtz, Paul Salm, Paul J. Taylor, and Stephen V. Lynch
- Subjects
Electrospray ,Chromatography ,medicine.diagnostic_test ,Chemistry ,Ultraviolet Rays ,Clinical Biochemistry ,Selected reaction monitoring ,Reproducibility of Results ,Ion suppression in liquid chromatography–mass spectrometry ,General Medicine ,Mass spectrometry ,High-performance liquid chromatography ,Sensitivity and Specificity ,Mass Spectrometry ,Therapeutic drug monitoring ,medicine ,Cyclosporine ,Protein precipitation ,Humans ,Drug Monitoring ,Chromatography, High Pressure Liquid ,Whole blood - Abstract
Objectives: Cyclosporin is an immunosuppressant drug with a narrow therapeutic window. Trough and 2-h post-dose blood samples are currently used for therapeutic drug monitoring in solid organ transplant recipients. The aim of the current study was to develop a rapid HPLC-tandem mass spectrometry (HPLC-MS) method for the measurement of cyclosporin in whole blood that was not only suitable for the clinical setting but also considered a reference method. Methods: Blood samples (50 mu L) were prepared by protein precipitation followed by C-18 solid-phase extraction while using d(12) cyclosporin as the internal standard. Mass spectrometric detection was by selected reaction monitoring with an electrospray interface in positive ionization mode. Results: The assay was linear from 10 to 2000 mu g/L (r(2) > 0.996, n = 9). Inter-day,analytical recovery and imprecision using whole blood quality control samples at 10, 30, 400, 1500, and 2000 mu g/L were 94.9-103.5% and
- Published
- 2004
21. Quantification and stability of everolimus (SDZ RAD) in human blood by high-performance liquid chromatography-electrospray tandem mass spectrometry
- Author
-
Paul J. Taylor, Peter I. Pillans, Paul Salm, and Stephen V. Lynch
- Subjects
Sirolimus ,Electrospray ,Spectrometry, Mass, Electrospray Ionization ,Chromatography ,Chemistry ,Clinical Biochemistry ,Selected reaction monitoring ,Reproducibility of Results ,Cell Biology ,General Medicine ,Reference Standards ,Mass spectrometry ,Tandem mass spectrometry ,Biochemistry ,High-performance liquid chromatography ,Analytical Chemistry ,Protein precipitation ,Humans ,Everolimus ,Quantitative analysis (chemistry) ,Chromatography, High Pressure Liquid ,Immunosuppressive Agents ,Whole blood - Abstract
We report here a validated method for the quantification of a new immunosuppressant drug, everolimus (SDZ RAD), using HPLC-tandem mass spectrometry. Whole blood samples (500 mul) were prepared by protein precipitation, followed by C-18 solid-phase extraction. Mass spectrometric detection was by selected reaction monitoring with an electrospray interface operating in positive ionization mode. The assay was linear from 0.5 to 100 mug/l (r(2) > 0.996, n = 9). The analytical recovery and inter-day imprecision, determined using whole blood quality control samples (n = 5) at 0.5, 1.2, 20.0, and 75.0 mug/l, was 100.3-105.4% and less than or equal to7.6%, respectively. The assay had a mean relative recovery of 94.8 +/- 3.8%. Extracted samples were stable for up to 24 h. Fortified everolimus blood samples were stable at -80 degreesC for at least 8 months and everolimus was found to be stable in blood when taken through at least three freeze-thaw cycles. The reported method provides accurate, precise and specific measurement of everolimus in blood over a wide analytical range and is currently supporting phase 11 and III clinical trials. (C) 2002 Elsevier Science B.V. All rights reserved.
- Published
- 2002
22. A cluster analysis of harmony in the McGill Billboard dataset
- Author
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Kris Shaffer, Esther Vasiete, Brandon Jacquez, Aaron Davis, Diego Escalante, Calvin Hicks, Joshua McCann, Camille Noufi, and Paul Salminen
- Subjects
mcgill billboard dataset ,pop/rock ,rock ,cluster analysis ,machine learning ,harmonic syntax ,transitional probability ,visualization ,Music ,M1-5000 - Abstract
We set out to perform a cluster analysis of harmonic structures (specifically, chord-to-chord transitions) in the McGill Billboard dataset, to determine whether there is evidence of multiple harmonic grammars and practices in the corpus, and if so, what the optimal division of songs, according to those harmonic grammars, is. We define optimal as providing meaningful, specific information about the harmonic practices of songs in the cluster, but being general enough to be used as a guide to songwriting and predictive listening. We test two hypotheses in our cluster analysis — first that 5–9 clusters would be optimal, based on the work of Walter Everett (2004), and second that 15 clusters would be optimal, based on a set of user-generated genre tags reported by Hendrik Schreiber (2015). We subjected the harmonic structures for each song in the corpus to a K-means cluster analysis. We conclude that the optimal clustering solution is likely to be within the 5–8 cluster range. We also propose that a map of cluster types emerging as the number of clusters increases from one to eight constitutes a greater aid to our understanding of how various harmonic practices, styles, and sub-styles comprise the McGill Billboard dataset.
- Published
- 2020
- Full Text
- View/download PDF
23. Accurate estimation of mycophenolic acid AUC
- Author
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Charlene Willis, Peter I. Pillans, Paul Salm, Susan E. Tett, and Paul J. Taylor
- Subjects
Pharmacology ,Antibiotics, Antineoplastic ,business.industry ,Accurate estimation ,Mycophenolic Acid ,Mycophenolic acid ,Transplantation ,Area Under Curve ,Medicine ,Humans ,Pharmacology (medical) ,business ,medicine.drug - Published
- 2001
24. Evaluation of microparticle enzyme immunoassay against HPLC-mass spectrometry for the determination of whole-blood tacrolimus in heart- and lung-transplant recipients
- Author
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M. Black, Peter I. Pillans, Paul J. Taylor, David M Rutherford, and Paul Salm
- Subjects
Drug ,Adult ,Male ,Adolescent ,medicine.medical_treatment ,media_common.quotation_subject ,Clinical Biochemistry ,chemical and pharmacologic phenomena ,Microparticle Enzyme Immunoassay ,Pharmacology ,Mass spectrometry ,Mass Spectrometry ,Tacrolimus ,Immunoenzyme Techniques ,medicine ,Lung transplantation ,Humans ,Chromatography, High Pressure Liquid ,media_common ,Whole blood ,Aged ,Heart transplantation ,Chromatography ,medicine.diagnostic_test ,Chemistry ,Reproducibility of Results ,General Medicine ,Middle Aged ,surgical procedures, operative ,Therapeutic drug monitoring ,Heart Transplantation ,Female ,Lung Transplantation - Abstract
Tacrolimus is an immunosuppressant drug with a narrow therapeutic window and thus requires therapeutic drug monitoring. This study evaluates the suitability of the second-generation microparticle enzyme immunoassay (MEIA II) against a specific method, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS), for the measurement of tacrolimus in both heart- and lung-transplant groups. A secondary objective was to investigate the effect of tacrolimus concentration on MEIA II measurement.The HPLC-MS assay was conducted as per our reported method and MEIA II performed according to manufacturer's instructions. Quality-control samples at 5, 11, and 22 microg/L were run in each batch to ensure assay integrity in both methods. Multiple trough samples from 18 heart patients (n = 126) and 17 lung patients (n = 203) were analyzed.The inter-batch imprecision and analytical recovery over the quality-control range by HPLC-MS (n = 12) was6% and 98.2% to 104%, respectively, and by MEIA II (n = 16)15% and 92.0% to 99.1%, respectively. The mean overestimation by MEIA II between the two methods for heart- and lung-transplant patient samples was found to be 9.9% (range: -37.4-45.4%) and 13.2% (range: -29.2-64.3%), respectively. Stratification of these data based on the tacrolimus concentration determined by MEIA II, yielded no statistically significant differences in bias between concentration subgroups within the clinically relevant range (p0.4). However, a statistically significant difference was detected between the highest concentration subgroup (20.0 microg/L) and lower concentration subgroups in both transplant populations (p0.05).This study suggests that where HPLC-MS is not available, MEIA II may be suitable for the therapeutic drug monitoring of tacrolimus in heart- and lung-transplant recipients. However, the clinical importance of the observed mean bias, considering the wide range in overestimation in heart- and lung-transplant patient samples, is yet to be determined.
- Published
- 2000
25. Quantification of free mycophenolic acid by high-performance liquid chromatography-atmospheric pressure chemical ionisation tandem mass spectrometry
- Author
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Susan E. Tett, Peter I. Pillans, Paul J. Taylor, Paul Salm, and Charlene Willis
- Subjects
Detection limit ,Chemical ionization ,Analyte ,Chromatography ,Chemistry ,Analytical chemistry ,General Chemistry ,Mycophenolic Acid ,Tandem mass spectrometry ,High-performance liquid chromatography ,Mass Spectrometry ,Atmospheric Pressure ,Liquid chromatography–mass spectrometry ,Humans ,Solid phase extraction ,Quantitative analysis (chemistry) ,Chromatography, High Pressure Liquid - Abstract
To facilitate the investigation of free mycophenolic acid concentrations we developed a high-performance liquid chromatography tandem mass spectrometry method using indomethacin as an internal standard. Free drug was isolated from plasma samples (500 mul) using ultrafiltration, The analytes were extracted from the ultrafiltrate (200 mul) using C-18 solid-phase extraction. Detection was by selected reactant monitoring of mycophenolic acid (m/z 318.9-->190.9) and the internal standard (m/z 356.0-->297.1) with an atmospheric pressure chemical ionisation interface. The total chromatographic analysis time was 12 min. The method was found to be linear over the range investigated, 2.5-200 mug/l (r>0.990, n=6). The relative recovery of the method for the control samples studied (7.5, 40.0 and 150 mug/l) ranged from 95 to 104%. The imprecision of the method, expressed in terms of intra- and inter-day coefficients of variation, was
- Published
- 2000
26. Evaluation of limited sampling strategies for estimation of 12-hour mycophenolic acid area under the plasma concentration-time curve in adult renal transplant patients
- Author
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Susan E. Tett, Paul Salm, Peter I. Pillans, Paul J. Taylor, and Charlene Willis
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Urology ,Models, Biological ,Mycophenolic acid ,Cohort Studies ,Pharmacokinetics ,Predictive Value of Tests ,Linear regression ,medicine ,Humans ,Pharmacology (medical) ,Aged ,Pharmacology ,Antibiotics, Antineoplastic ,Models, Statistical ,medicine.diagnostic_test ,business.industry ,Area under the curve ,Linear model ,Middle Aged ,Mycophenolic Acid ,Kidney Transplantation ,Surgery ,Transplantation ,Therapeutic drug monitoring ,Area Under Curve ,Linear Models ,Female ,Drug Monitoring ,business ,medicine.drug ,Blood sampling - Abstract
Mycophenolate mofetil, the oral prodrug of mycophenolic acid, is indicated as immunosuppressive therapy after renal transplantation. To aid in the investigation of pharmacokinetic-pharmacodynamic relationships of mycophenolic acid in the clinical setting, limited blood sampling strategies have been proposed, and models from these developed, for the estimation of mycophenolic acid area under the concentration-time curve (AUC). In the current study, the authors investigated the predictive performance of six published models to estimate AUC. A total of 49 profiles from 25 renal transplant patients were used to test each model's performance against a full 14 time-point AUC. A wide range of agreement was found when predicted AUCs were compared with full AUCs using linear regression analysis (range: r2 = 0.499 to 0.836). Model 1, which uses 4 time-points over 6 hours, was found to be superior to all other models. The range of time-points used in this model takes into account patients with variable absorption. This model should be further tested on data sets from other centers. The relatively poor performance of the other models may be caused by their inability to describe the peak concentration in these patients. Caution is warranted when using limited sampling strategies on patients whose absorption of mycophenolic acid is altered, compared with those of the pharmacokinetic profiles from which the model was developed.
- Published
- 2000
27. Simultaneous quantification of tacrolimus and sirolimus, in human blood, by high-performance liquid chromatography-tandem mass spectrometry
- Author
-
Paul Salm, Stephen V. Lynch, Paul J. Taylor, and Peter I. Pillans
- Subjects
Male ,Tandem mass spectrometry ,High-performance liquid chromatography ,Sensitivity and Specificity ,Drug Administration Schedule ,Mass Spectrometry ,Tacrolimus ,Pharmacokinetics ,medicine ,Humans ,Pharmacology (medical) ,Chromatography, High Pressure Liquid ,Pharmacology ,Detection limit ,Sirolimus ,Chromatography ,medicine.diagnostic_test ,Chemistry ,Selected reaction monitoring ,Organ Transplantation ,surgical procedures, operative ,Therapeutic drug monitoring ,Female ,Drug Monitoring ,Quantitative analysis (chemistry) ,Immunosuppressive Agents ,medicine.drug - Abstract
In this paper the authors present a validated method for the simultaneous analysis of tacrolimus and sirolimus in human blood by high-performance liquid chromatography-electrospray tandem mass spectrometry. Blood samples (500 microL) were prepared by C18 solid-phase extraction. Mass spectrometric detection was by selected reaction monitoring. The assay was linear for both compounds over the range 0.25-100 microg/L (r2 > 0.996, n = 7). At the limit of quantification (0.25 microg/L), for both sirolimus and tacrolimus, the interday imprecision was < 3% and the analytical recovery was between 97.0% and 102%, respectively. The interbatch and intrabatch coefficients of variation of the method for both analytes, at the three quality control concentrations (0.5, 20, and 80 microg/L), were < 16% and < 10%, respectively. The analytical recovery, at the three control concentrations, ranged from 99.2% to 104% of the nominal concentration. The mean absolute recovery (+/- standard deviation) of tacrolimus, sirolimus, and internal standard was 82 +/- 7%, 89 +/- 12%, and 77 +/- 8%, respectively (n = 12). In conclusion, the method presented can be used for simultaneous determination of tacrolimus and sirolimus and will aid in pharmacokinetic studies and therapeutic drug monitoring of these drugs. Furthermore, this method has economic benefits in the clinical setting where these drugs are coadministered.
- Published
- 2000
28. Evaluation Of A Fluorescent Polarization Immunoassay (Fpia) For Whole Blood Everolimus Determination In Renal Transplant Recipients
- Author
-
Christopher Warnholtz, Paul J. Taylor, Jared Boyd, Paul Salm, Peter Marbach, and Lili Arabshahi
- Subjects
Pharmacology ,medicine.medical_specialty ,Everolimus ,medicine.diagnostic_test ,business.industry ,Fluorescent polarization ,Urology ,Renal transplant ,Immunoassay ,medicine ,Pharmacology (medical) ,business ,Whole blood ,medicine.drug - Published
- 2005
29. Comparison Of The Re-introduced MEIA?? Sirolimus Assay With HPLC-MSMS In Renal Transplant Recipients
- Author
-
Fiona A Wicks, Paul Salm, Raymond G. Morris, Paul J. Taylor, and A Theodossi
- Subjects
Pharmacology ,medicine.medical_specialty ,business.industry ,Renal transplant ,Sirolimus ,Urology ,Medicine ,Pharmacology (medical) ,business ,High-performance liquid chromatography ,medicine.drug - Published
- 2005
30. A reliable high-performance liquid chromatography assay for high-throughput routine cyclosporin A monitoring in whole blood
- Author
-
Paul Salm, Peter J. Ravenscroft, Ross Norris, D. E. Davis, and Paul J. Taylor
- Subjects
Pharmacology ,Chromatography ,medicine.diagnostic_test ,Chemistry ,Extraction (chemistry) ,Reference Standards ,High-performance liquid chromatography ,Standard curve ,Cyclosporin D ,Therapeutic drug monitoring ,Cyclosporin a ,Chemistry, Clinical ,medicine ,Cyclosporine ,Humans ,Pharmacology (medical) ,Solid phase extraction ,Drug Monitoring ,Chromatography, High Pressure Liquid ,Whole blood - Abstract
We report here a reliable high-performance liquid chromatography-ultraviolet assay for routine assay of cyclosporin A (CsA) in whole blood using solid-phase extraction. This assay is linear, between 20 and 2,000 micrograms/L, with correlation coefficients0.998 for five consecutive standard curves. All coefficients of variation (CV) were8% at CsA concentrations of 45, 480, and 1,800 micrograms/L, with the exception of the between-day CV at 45 micrograms/L, which was15%. The relative accuracy of the method is94% at 45, 480, and 1,800 micrograms/L. The mean recoveries for CsA and cyclosporin D (internal standard) were 38.2 +/- 4.8% (n = 45) and 40.1 +/- 6.7% (n = 45), respectively. This method has proven to be reliable and robust in a high-throughput therapeutic drug monitoring laboratory.
- Published
- 1993
31. Single-Point Calibration for Sirolimus Quantification
- Author
-
Paul J. Taylor, Paul Salm, Kimberley K. Forrest, and Peter I. Pillans
- Subjects
Quality Control ,Sirolimus ,Pharmacology ,Chromatography ,Calibration (statistics) ,business.industry ,Tandem mass spectrometry ,Calibration ,medicine ,Humans ,Pharmacology (medical) ,Single point ,business ,Immunosuppressive Agents ,medicine.drug - Published
- 2001
32. Measurement of dothiepin and its major metabolites in plasma by high-performance liquid chromatography
- Author
-
Paul J. Taylor, Paul Salm, Bruce G. Charles, Peter J. Ravenscroft, and Ross Norris
- Subjects
Analyte ,Chromatography ,Coefficient of variation ,Analytical chemistry ,Reproducibility of Results ,General Chemistry ,Plasma ,Trimipramine ,Reference Standards ,High-performance liquid chromatography ,chemistry.chemical_compound ,chemistry ,Dothiepin ,medicine ,Humans ,Sample preparation ,Diethyl ether ,Quantitative analysis (chemistry) ,Chromatography, High Pressure Liquid ,medicine.drug - Abstract
This paper describes a reversed-phase high-performance liquid chromatographic method which will simultaneously measure dothiepin and its three major metabolites (northiaden, northiaden-S-oxide and dothiepin-S-oxide) in plasma using trimipramine as internal standard. Sample preparation involved a basic extraction using diethyl ether followed by an acid back-extraction. The method we report is linear over the range 50-1000 ng/ml (r = 0.999), for all analytes. Total imprecision is less than 11% (coefficient of variation) and accuracy is greater than 94% (n = 20). Recovery of analytes varied considerably from 51.7% for northiaden-S-oxide to 90.2% for dothiepin-S-oxide.
- Published
- 1992
33. Evaluation Of Internal Standards For The Measurement Of Cyclosporin A By Hplc-esi-ms/ms
- Author
-
Stephen V. Lynch, Paul J. Taylor, Paul Salm, Donald P. Cooper, Scott R Brown, and Peter I. Pillans
- Subjects
Pharmacology ,Chromatography ,business.industry ,Cyclosporin a ,Medicine ,Hplc esi ms ms ,Pharmacology (medical) ,business - Published
- 2005
34. Measurement Of Fty720 By Hplc-apci-tandem Mass Spectrometry
- Author
-
Christopher Warnholtz, Michael Chan, Stephen V. Lynch, Paul Salm, and Paul J. Taylor
- Subjects
Pharmacology ,Ion-mobility spectrometry–mass spectrometry ,Chromatography ,Protein mass spectrometry ,Chemistry ,Selected reaction monitoring ,Thermospray ,Pharmacology (medical) ,Tandem mass spectrometry ,Top-down proteomics ,Sample preparation in mass spectrometry ,Mass spectrometry imaging - Published
- 2005
35. New Cedia?? Sirolimus Assay Compared With Lcmsms And Hplc/uv In Samples From Renal Transplant Recipients
- Author
-
Raymond G. Morris, M J James, Paul J. Taylor, Ian S. Westley, and Paul Salm
- Subjects
Pharmacology ,Chromatography ,business.industry ,Renal transplant ,Sirolimus ,medicine ,Pharmacology (medical) ,business ,medicine.drug - Published
- 2005
36. COMPARISON OF HPLC-TANDEM MASS SPECTROMETRY (LC-MS) AND MICROPARTICLE ENZYME IMMUNOASSAY (MEIA) FOR THE DETERMINATION OF WHOLE BLOOD TACROLIMUS IN HEART AND LUNG TRANSPLANT PATIENTS
- Author
-
M. Black, Peter I. Pillans, Paul J. Taylor, D M Rutherford, and Paul Salm
- Subjects
Pharmacology ,Lung ,Chemistry ,Microparticle Enzyme Immunoassay ,Tandem mass spectrometry ,High-performance liquid chromatography ,Tacrolimus ,medicine.anatomical_structure ,Liquid chromatography–mass spectrometry ,medicine ,Pharmacology (medical) ,Transplant patient ,Whole blood - Published
- 1999
37. THE PHARMACOKINETICS OF TOTAL AND FREE MYCOPHENOLIC ACID IN ADULT RENAL TRANSPLANT RECIPIENTS
- Author
-
Paul Salm, Peter I. Pillans, Russell J. Rigby, and Paul J. Taylor
- Subjects
Pharmacology ,medicine.medical_specialty ,Pharmacokinetics ,business.industry ,Renal transplant ,Urology ,medicine ,Pharmacology (medical) ,business ,Mycophenolic acid ,medicine.drug - Published
- 1999
38. SIMULTANEOUS DETERMINATION OF TACROLIMUS AND SIROLIMUS BY LIQUID CHROMATOGRAPHY TANDEM MASS SPECTROMETRY (HPLC-MS/MS)
- Author
-
Peter I. Pillans, Stephen V. Lynch, Paul Salm, and Paul J. Taylor
- Subjects
Pharmacology ,Chromatography ,Chemistry ,Liquid chromatography–mass spectrometry ,Sirolimus ,medicine ,Pharmacology (medical) ,Tacrolimus ,medicine.drug - Published
- 1999
39. EVALUATION OF A MICROPARTICLE ENZYME IMMUNOASSAY (MEIA) FOR WHOLE BLOOD SIROLIMUS DETERMINATION IN RENAL TRANSPLANT RECIPIENTS
- Author
-
Paul J. Taylor, Peter I. Pillans, and Paul Salm
- Subjects
Pharmacology ,medicine.medical_specialty ,Renal transplant ,business.industry ,Sirolimus ,medicine ,Urology ,Pharmacology (medical) ,Microparticle Enzyme Immunoassay ,business ,Whole blood ,medicine.drug - Published
- 1999
40. THE ANALYTICAL PERFORMANCE OF HPLC-TANDEM MASS SPECTROMETRY (LC-MS) AND MICROPARTICLE ENZYME IMMUNOASSAY (MEIA) FOR SIROLIMUS WHOLE BLOOD MEASUREMENT
- Author
-
Paul Salm, Paul J. Taylor, and Peter I. Pillans
- Subjects
Pharmacology ,Chromatography ,Chemistry ,Liquid chromatography–mass spectrometry ,Sirolimus ,medicine ,Pharmacology (medical) ,Microparticle Enzyme Immunoassay ,Tandem mass spectrometry ,High-performance liquid chromatography ,medicine.drug ,Whole blood - Published
- 1999
41. Accuracy of physical self-description among chronic exercisers and non-exercisers
- Author
-
Joseph M. Berning, Mark DeBeliso, Trish G. Sevene, Kent J. Adams, Paul Salmon, and Bryant A. Stamford
- Subjects
Medicine ,Mental healing ,RZ400-408 - Abstract
This study addressed the role of chronic exercise to enhance physical self-description as measured by self-estimated percent body fat. Accuracy of physical self-description was determined in normal-weight, regularly exercising and non-exercising males with similar body mass index (BMI)’s and females with similar BMI’s (n=42 males and 45 females of which 23 males and 23 females met criteria to be considered chronic exercisers). Statistical analyses were conducted to determine the degree of agreement between self-estimated percent body fat and actual laboratory measurements (hydrostatic weighing). Three statistical techniques were employed: Pearson correlation coefficients, Bland and Altman plots, and regression analysis. Agreement between measured and self-estimated percent body fat was superior for males and females who exercised chronically, compared to non-exercisers. The clinical implications are as follows. Satisfaction with one’s body can be influenced by several factors, including self-perceived body composition. Dissatisfaction can contribute to maladaptive and destructive weight management behaviors. The present study suggests that regular exercise provides a basis for more positive weight management behaviors by enhancing the accuracy of self-assessed body composition.
- Published
- 2014
- Full Text
- View/download PDF
42. Investigating the Factors Influencing Cyclist Awareness and Behaviour: An On-Road Study of Cyclist Situation Awareness
- Author
-
Paul Salmon, Michael Lenné, Guy Walker, and Ashleigh Filtness
- Subjects
Transportation and communications ,HE1-9990 - Abstract
Situation awareness, one’s understanding of ‘what is going on’, is a critical commodity for road users. Although the concept has received much attention in the driving context, situation awareness in vulnerable road users, such as cyclists, remains unexplored. This paper presents the findings from an exploratory on-road study of cyclist situation awareness, the aim of which was to explore how cyclists develop situation awareness, what their situation awareness comprises, and what the causes of degraded cyclist situation awareness may be. Twenty participants cycled a pre-defined urban on-road study route. A range of data were collected, including verbal protocols, forward scene video and rear video, and a network analysis procedure was used to describe and assess cyclist situation awareness. The analysis produced a number of key findings regarding cyclist situation awareness, including the potential for cyclists’ awareness of other road users to be degraded due to additional situation awareness and decision making requirements that are placed on them in certain road situations. Strategies for improving cyclists’ situation awareness are discussed.
- Published
- 2013
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