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Sofosbuvir (SOF) and daclatasvir (DCS) are novel, recently developed direct acting antiviral agents characterized by potent anti-hepatitis C virus action. A fast and efficient HPLC-UV method was developed, validated and applied for simultaneous determination of SOF and DCS in pharmaceutical formulations and biological fluids based on coupling liquid-liquid extraction with ultrasound and dual wavelength detection at λ max ; 260 and 313 nm for SOF and DCS, respectively. This approach provided simple, sensitive, specific and cost-effective determination of the SOF-DCS mixture with good recoveries of the analytes from plasma. Analytes were separated within 7 min on C 18 analytical column with acetonitrile-10 mM acetate buffer of pH 5.0 at a flow rate of 1.0 mL min -1 . The linear ranges were 1-20 μg mL -1 for SOF and 0.6-6 μg mL -1 for DCS with correlation coefficients ≥0.9995. The detection limits in spiked rabbit plasma were 0.20 and 0.19 μg mL -1 for SOF and DCS, respectively. The method was validated according to ICH and US-FDA guidelines. Finally, the method was successfully applied for simultaneous pharmacokinetic studies of SOF and DCS in rabbits using rofecoxib as internal standard., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Bisphenol S (BPS) has been introduced as a substitute for bisphenol A (BPA), and widely used in the manufacture of polycarbonate plastics, epoxy resins and thermal papers. Despite its adverse health outcomes and widespread exposure, pharmacokinetic data of BPS are not available for either animals or humans. The objective of the study is to describe pharmacokinetic characteristics of BPS in human body after a single oral administration with a compartmental pharmacokinetic model. Seven healthy young adults were orally exposed to 8.75μg/bw of d 4 -BPS, and serum and urine samples were collected for 48h. The concentrations of total and unconjugated d 4 -BPS in samples were measured using HPLC-MS/MS. Based on the time-concentration profiles in serum and urine, non-compartmental analysis was performed, and two-compartment model was constructed and validated. As a result of non-compartmental analysis, total d 4 -BPS was rapidly absorbed within 1h (0.7±0.3h) after oral administration, and excreted in urine with terminal half-life of <7h (6.8±0.7h). Fractional urinary excretion (F ue ) of total d 4 -BPS for 48h was 92±17% (67-104%) for men and 70±36% (59-77%) for women. The two-compartment model well described pharmacokinetic properties of BPS, and its parameter estimates were consistent with those from non-compartmental analysis. This study provides information on absorption, distribution, metabolism and elimination of BPS in human body, and the pharmacokinetic model can be utilized for estimating exposure dose of BPS, contributing to more realistic exposure assessment., (Copyright © 2017. Published by Elsevier Ltd.)

The natural variability of gastric pH or gastric acid reducing medications can result in lower and more variable clinical pharmacokinetics for basic compounds in patient populations. Progressing alternative salt forms with improved solubility and dissolution properties can minimise this concern. This manuscript outlines a nonclinical approach comprising multiple biopharmaceutical, in vitro and physiologically based pharmacokinetic model (PBPK) modelling studies to enable selection of an alternative salt form for danirixin (DNX, GSK1325756), a pharmaceutical agent being developed for chronic obstructive pulmonary disease (COPD). The hydrobromide salt of DNX was identified as having superior biopharmaceutical properties compared to the free base (FB) form in clinical development and the impact of switching to the hydrobromide salt (HBr) was predicted by integrating the nonclinical data in a PBPK model (using GastroPlus™) to enable simulation of clinical drug exposure with FB and HBr salts in the absence and presence of a gastric acid reducing comedication (omeprazole, a proton pump inhibitor (PPI)). Subsequent investigation of DNX pharmacokinetics in a Phase 1 clinical study comparing FB with HBr salt forms confirmed that DNX HBr had reduced the variability of drug exposure and that exposure was not affected by PPI co-administration with DNX HBr. This case study therefore adds to the surprisingly few examples of a more soluble salt of a weak base translating to an improvement in human pharmacokinetics and illustrates a clear clinical benefit of salt selection during drug development., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Somatostatin (SST) is a peptide hormone that regulates the endocrine system and affects neurotransmission via interaction with G protein-coupled SST receptors and inhibition of the release of different hormones. The aim of this study was to investigate whether the analgesic properties of the selective SSTR4 agonist J-2156 are mediated via peripheral and/or spinal receptors. Effect on mechanical hyperalgesia in the Complete Freund׳s Adjuvant (CFA) model was measured after intraperitoneal application of J-2156. Electrophysiological neuronal recordings were conducted 24 h after injection of CFA or vehicle into the paw of Wistar rats. Mechanosensitivity of peripheral afferents of the saphenous nerve as well as of spinal wide dynamic range (WDR) and nociceptive-specific (NS) neurons were measured after systemic or spinal application of J-2156. In CFA animals J-2156 dose dependently reduced hyperalgesia in behavioral studies. The minimal effective dose was 0.1 mg/kg. Mechanosensitivity of peripheral afferents and spinal neurons was significantly reduced by J-2156. NS neurons were dose dependently inhibited by J-2156 while in WDR neurons only the highest concentration of 100 µM had an effect. In sham controls, J-2156 had no effect on neuronal activity. We demonstrated that J-2156 dose-dependently reduces peripheral and spinal neuronal excitability in the CFA rat model without affecting physiological pain transmission. Given the high concentration of the compound required to inhibit spinal neurons, it is unlikely that the behavioral effect seen in CFA model is mediated centrally. Overall these data demonstrated that the analgesic effect of J-2156 is mediated mainly via peripheral SST4 receptors., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A simultaneous, selective, sensitive, and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of bosentan, ambrisentan, sildenafil, and tadalafil in 50μL of human blood plasma. Diluted plasma samples were extracted using a solid-phase extraction procedure with 2% formic acid and methanol. The four drugs were separated by high-performance liquid chromatography using a C18 column and an isocratic mobile phase running at a flow rate of 0.2mL/min for 5min. The drugs were detected by a tandem mass spectrometer with electrospray ionization using deuterated compounds as internal standards. Calibration curves were generated over the linear concentration range of 2-1000ng/mL in plasma with a lower limit of quantification of 2ng/mL for all compounds. Finally, this validated method was applied to a clinical pharmacokinetic study in pediatric patients with pulmonary arterial hypertension (PAH) following the oral administration of PAH drugs. These results indicate that this method is suitable for assessing the risk/benefit of combination therapy in the pediatric population and useful for therapeutic drug monitoring for PAH treatment., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This work proposes a liquid chromatography-electrospray ionization ion trap mass spectrometry (LC-ESI-ITMS) method, for the quantification of sildenafil (SDF), tadalafil (TDF) and vardenafil (VDF) and their metabolites N-desmethylSDF, O-desethylSDF and N-desethylVDF, preceded by a sample preparation step based on protein and phospholipid elimination. A C8 column (150 mm × 4.6 mm, 5 μm) with ammonium formate (20mM) and acetonitrile as the mobile phase components have been used. This method has been validated, obtaining limits of quantification ranged from 1 to 2.5 ng/mL and 2 to 5 ng/g in serum and brain tissue respectively, while limits of detection ranged from 0.3 to 0.9 ng/mL in serum and 0.6 to 1.9 ng/g in brain tissue. Assay recoveries for low level QC samples were higher than 83% and the matrix effect ranged between 91% and 108% in serum and between 98% and 107% in brain tissue. The method has been applied to the quantification of these compounds in the serum and brain tissue of rats treated intraperitoneally with 10 mg/kg of SDF, TDF or VDF., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A sensitive and selective method for the simultaneous determination of non-steroidal anti-inflammatory drugs in bovine plasma was developed. Confirmatory analysis was carried out by liquid chromatography coupled with an electrospray ionisation tandem mass spectrometer (LC-ESI-MS/MS). Target compounds were acidified in plasma and extracted with acetonitrile. Sodium chloride was added to assist separation of the plasma and acetonitrile mixture. The acetonitrile extract is then subjected to liquid-liquid purification by the addition of hexane. Accuracy of the methods in plasma was between 93 and 102%. The precision of the method for the basic NSAIDs in plasma expressed as % RSD, for the within-laboratory reproducibility was less than 10%. Decision limit (CCα values) and detection capability (CCβ) values were established. The methods were validated according to Commission Decision 2002/657/EC., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Anion efflux transporters are expected to minimize target tissue delivery of N-[4-(benzoylaminophenyl)sulfonyl]glycine (BAPSG), a novel carboxylic acid aldose reductase inhibitor, which exists as a monocarboxylate anion at physiological conditions. Therefore, the objective of this study was to determine whether BAPSG delivery to various eye tissues including the retina and the brain can be enhanced by probenecid, a competitive inhibitor of anion transporters. To determine the influence of probenecid on eye and brain distribution of BAPSG, probenecid was administered intraperitoneally (120 mg/kg body weight; i.p.) 20 min prior to BAPSG (50 mg/kg; i.p.) administration. Drug disposition in various eye tissues including the retina and the brain was determined at 15 min, 1, 2 and 4h after BAPSG dose in male Sprauge-Dawley rats. To determine whether probenecid alters plasma clearance of BAPSG, influence of probenecid (120 mg/kg; i.p.) on the plasma pharmacokinetics of intravenously administered BAPSG (15 mg/kg) was studied as well. Finally, the effect of probenecid co-administration on the ocular tissue distribution of BAPSG was assessed in rabbits following topical (eye drop) administration. Following pretreatment with probenecid in the rat study, retinal delivery at 1h was increased by about 11-fold (2580 ng/g vs. 244 ng/g; p<0.05). Further, following probenecid pretreatment, significant BAPSG levels were detectable in the brain (45 + or - 20 ng/g) at 1h, unlike controls where the drug was not detectable. Plasma concentrations, plasma elimination half-life, and total body clearance of intravenously administered BAPSG were not altered by i.p. probenecid pretreatment. In the topical dosing study, a significant decline in BAPSG delivery was observed in the iris-ciliary body but no significant changes were observed in other tissues of the anterior segment of the eye including tears. Thus, inhibition of anion transporters is a useful approach to elevate retinal and brain delivery of BAPSG., (Copyright 2009 Elsevier Inc. All rights reserved.)

The determination of two sulphur-containing drugs, the COX-2 inhibitors celecoxib and etoricoxib, in the serum and synovial fluid of inflammatory arthritis patients, is described using a sensitive ultra performance liquid chromatography-inductively coupled plasma mass spectroscopy (UPLC/ICPMS) method. Confirmation of the identity of the analytes in the samples was also performed by electrospray quadruple time-of-flight mass spectrometry in positive electrospray ionisation mode. The two COX-2 inhibitors were extracted from serum and synovial fluid following dilution with acetate buffer (pH 5) and liquid-liquid extraction (LLE) into ethyl acetate. Extracted samples were then analysed using UPLC/ICPMS with sulphur-specific detection. The limit of detection by UPLC/ICPMS was 0.45 ng/ml of sulphur in both serum and synovial fluid. The UPLC/ICPMS method was applied to the analysis of samples from patients receiving either 200 mg/day of celecoxib (2x 100 mg), 90 mg/day etoricoxib or placebo. The range of concentrations detected in the samples for the two drugs was from 0.3 to 3.3 microg/ml.

The purpose of the present study was to determine sildenafil and a novel PDE-5 inhibitor, mirodenafil in the plasma and corpus cavernosum tissue of rats to compare their pharmacokinetic properties. The concentrations of mirodenafil and sildenafil in the rat plasma and corpus cavernosum tissue samples were analyzed using LC-MS/MS after a single oral administration at a dose of 40mg/kg to rats. Although the T(max), Tlambda(1/2) and MRT were not different between mirodenafil and sildenafil, the C(max) and AUC of mirodenafil were significantly higher than those of sildenafil in the plasma and corpus cavernosum tissue. Consequently mirodenafil remained longer than sildenafil in the plasma and tissue. This may provide pharmacokinetic evidence for assessment of the in vivo efficacy of mirodenafil and sildenafil.

Coupled-column separation using restricted access media as the first dimension in order to exclude macromolecules and retain micromolecules has been successfully used for a number of biological fluids. This paper describes the first method developed and validated for the analysis in a single run of the enantiomers of modafinil and its two major metabolites. The method was developed using a bidimensional HPLC system by coupling a restricted access medium (RAM) bovine serum albumin (BSA) column (1.0 cm x 0.46 cm i.d.) to an amylose tris[(S)-1-phenylethylcarbamate] chiral column. The method was fully validated and showed good linearity, precision, accuracy, sensitivity and selectivity, allowing it to be used for pharmacokinetic studies. The quality of the performance of both columns was maintained with over 280 plasma injections of 100 microl.

5-Ethyl-2-{5-[4-(2-hydroxyethyl)piperazine-1-sulfonyl]-2-propoxyphenyl}-7-propyl-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-one (SK3530) is a new phosphodiesterase type-5 inhibitor currently undergoing a Phase III investigation for the treatment of male erectile dysfunction. This study first describes a rapid and sensitive LC/MS/MS assay method for the quantification of SK3530 and its major metabolite, SK3541, in human plasma. The assay was validated to demonstrate the specificity, linearity, recovery, lower limit of quantification (LLOQ), accuracy, and precision. The multiple reaction monitoring was based on the transition of m/z=532.5-->99.1 for SK3530, 488.6-->295.5 for SK3541, and 520.3-->99.1 for SK3304 (internal standard). The assay utilized a single liquid-liquid extraction and isocratic elution, and the LLOQ was 1 ng/ml using 0.2 ml human plasma. The assay was linear over a range from 1 to 1000 ng/ml for both SK3530 and SK3541, with correlation coefficients >0.9999. The mean intra- and inter-day assay accuracy ranged from 94.7 to 101.6% and 96.8 to 101.1% for SK3530 and 92.6-105.7% and 97.4-107.8% for SK3541, respectively. The mean intra- and inter-day precision was between 7.2-12.1% and 5.7-7.4% for SK3530 and 4.6-13.2% and 5.0-14.1% for SK3541, respectively. The developed assay was applied to a clinical pharmacokinetic study after oral administration of SK3530 in healthy male volunteers (dose 100 mg).

A simple, sensitive and specific liquid chromatography/tandem mass spectrometry method for the quantitation of aildenafil, a new phosphodiesterase V inhibitor, in human plasma is presented. The analyte and internal standard, sildenafil, were extracted by a one-step liquid-liquid extraction in alkaline conditions and separated on a C(18) column using ammonia:10mM ammonium acetate buffer:methanol (0.1:15:85, v/v/v) as the mobile phase. The detection by an API 4000 triple quadrupole mass spectrometer in multiple-reaction monitoring mode was completed within 2.5 min. The calibration curve exhibited a linear dynamic range of 0.05-100 ng/ml with a 10 pg/ml limit of detection. The intra- and inter-day precisions measured as relative standard deviation were within 8.04% and 5.72%, respectively. This method has been used in a pharmacokinetic study of aildenafil in healthy male volunteers each given an oral administration of one of the three dosages.

A method which employed high-performance liquid chromatography coupled with electrochemical detection was developed for the simultaneous determination of sildenafil and its metabolite, N-desmethyl sildenafil, in human plasma has. The method was developed and validated for purposes of its application to a pharmacokinetic study in healthy volunteers after an oral dose of 50mg/tablet under fasting conditions. High precision and accuracy were demonstrated. A one-step liquid-liquid extraction further provides a simple and practical way to process plasma samples containing sildenafil with good quantitative recovery. Sampling lasted for 24h after dosing; consequently a limit of quantitation (LOQ) of 7.858 ng/mL was achieved for sildenafil whereas a LOQ of 8.675 ng/mL was obtained for N-desmethyl sildenafil. The mobile phase consisted of acetonitrile, methanol and phosphate buffer (0.05 M) (18.5:34.5:47.0, v/v/v) pH 7.68. The stationary phase was a C(8) (150 mm x 4.6 mm), 5 microm particle size operated at 27 degrees C. All analytes were stable at the pH of the supernatant, and during the analytical time window. At the applied potential of +1.20 V versus Ag/AgCl, no interferences from endogenous plasma compounds were recorded at the retention times of sildenafil, N-desmethyl sildenafil. High resolution was obtained between the analytes and the employed internal standards.

There are many reports concerning the physiological and pathological involvement of cyclooxygenase (COX)-2 in the central nervous system and peripheral tissue cells. Selective COX-2 inhibitors that mainly distribute peripherally have not been reported thus far. Therefore central and peripheral roles of COX-2 remain classified pharmacologically. In this study, in vivo pharmacological profiles of CIAA ([6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]acetic acid), a novel selective COX-2 inhibitor which distributes at higher concentrations in plasma than in brain, were compared with those of well-known selective COX-2 inhibitors, celecoxib and rofecoxib. Additionally, the possibility of pharmacological separation between peripheral and central actions of COX-2 with the inhibitors was investigated. CIAA selectively inhibited COX-2 activity compared with COX-1 in in vitro assays with rat whole blood. The compound exhibited lower brain penetration and higher plasma concentration (the brain/plasma concentration ratio was approximately 0.02) than celecoxib and rofecoxib after oral administration. Therefore, CIAA is mainly expected to act peripherally. Edema and prostaglandin E2 (PGE2) production in Carrageenan-injected rat paws, and pyrexia and PGE2 production in the brain in lipopolysaccharide (LPS)-injected rats were measured in in vivo experiments. CIAA exhibited lower ratios of anti-pyretic/anti-edematous activities and of inhibitory activities of PGE2 production in brain/paw than those of celecoxib and rofecoxib, and these ratios well-reflected brain/plasma concentration ratios. In conclusion, we discovered a novel selective COX-2 inhibitor, CIAA, which distributes at higher concentrations in plasma than in brain, which would make possible the pharmacological separation of the peripheral and central functions of COX-2.

HPLC method for the determination of sildenafil and its metabolite (N-demethylsildenafil) in rat serum has been developed. The technique included a solid phase extraction of the serum samples on a [poly(divinylbenzene-co-N-vinylpyrrolidone)] solid phase extraction sorbent. After conditioning, the cartridge was loaded with 0.5 mL of buffered serum containing internal standard. Elution was made with 1 mL of acetonitrile. After evaporation of the eluates to dryness and reconstitution with methanol, the samples were analyzed on Kromasil C18 column phase with phosphate buffer 0.05 M/acetonitrile: 54/46, pH 8. Detection was carried out using a photodiode array detector. For sildenafil and demethylsildenafil, full validation of the proposed method was provided (linearity range, calibration curves, average extraction efficiency; average intra-day and interday variabilities, limit of detection, limit of quantification, specificity). The proposed method was successfully utilised to quantify sildenafil and N-demethylsidenafil in rat serum for a pharmacokinetic study.

HOE642 (4-isopropyl-3-methylsulphonylbenzoyl-guanidine methanesulphonate), a novel Na(+)-H+ exchange subtype 1 inhibitor, was investigated for its possible antiarrhythmic effects on coronary artery ligation/reperfusion and ouabain-induced arrhythmias in the canine heart which may occur after intracellular Ca2+ overload. Also, the effects of HOE642 on coronary artery ligation/reperfusion of the left coronary artery were tested in rat hearts. HOE642 (1 mg/kg) significantly suppressed the occurrence of fatal ventricular fibrillation during coronary artery ligation and after reperfusion in dogs (2 out of 8 dogs in the treated group compared to 7 out of 8 dogs in the control group, P < 0.05), but did not suppress ventricular premature contractions and ventricular tachycardia during ischemia in the canine hearts. HOE642 at the same dose markedly reduced the total duration and the incidence of reperfusion-induced ventricular tachycardia, and the incidence and mortality of reperfusion-induced ventricular fibrillation in rats (ventricular tachycardia duration, 159 +/- 12 s to 21 +/- 8 s, P < 0.01; ventricular tachycardia, 100% to 69%; ventricular fibrillation, 89% to 0%, P < 0.01; mortality, 89% to 11%, P < 0.01). The heart rate, blood pressure, QT interval and ST segment did not change in the canine and rat hearts. HOE642 slightly decreased the arrhythmic ratio of the ouabain-induced arrhythmia only at two time points (28 and 35 min after injection) in the canine hearts. In conclusion, HOE642 has obvious antifibrillatory effects on ischemia/reperfusion arrhythmias and, in addition, has a weak suppressing effect on the ouabain-induced arrhythmia.

Previous studies have demonstrated that cytochrome P450 2E1 (P450 2E1) catalyzes the oxidation of acetone in vitro. The present study was designed to determine the importance of P450 2E1 in the catabolism of acetone in rats using diallyl sulfide (DAS) as an inhibitor of this enzyme. After a single intragastric dose of DAS, blood samples were collected from rats at different time points, and blood acetone concentrations were measured by gas chromatography. In a low DAS dose (50 mg/kg body weight) group, the maximum acetone level of 6-fold higher than the normal level was reached at 6 hr; the acetone level returned to normal at 48 hr. In a high dose (200 mg/kg) group, the maximum acetone level of 9-fold higher than the normal level was reached at 12 hr; the acetone level returned to normal at 60 hr. The turnover time and fractional turnover rate of elevated acetone were 15.8 +/- 0.5 hr and 0.054 +/- 0.001 hr-1, respectively, for the low dose, and 19.2 +/- 0.6 hr and 0.046 +/- 0.005 hr-1, respectively, for the high dose. In a chronic experiment, DAS (50 and 200 mg/kg, i.g.) was given to rats daily for 29 days, and elevated blood acetone levels were observed during the entire experimental period: 2.0 to 2.8 micrograms/mL for the low dose and 3.4 to 3.9 micrograms/mL for the high dose at 24 hr after the 1st, 7th, 14th and 28th doses versus 0.8 to 0.9 micrograms/mL for the control. The increase of blood acetone level was closely related to the decreases of N-nitrosodimethylamine (NDMA) demethylase activity and P450 2E1 content in liver microsomes. Consistent with the lack of cumulative effect from the multiple doses of DAS on acetone level, rather stable levels of the DAS metabolites, diallyl sulfoxide (45.0 micrograms/mL, range: 33.8 to 58.6 micrograms/mL) and diallyl sulfone (11.7 micrograms/mL, range: 6.9 to 15.6 micrograms/mL), were observed at 24 hr after the 1st, 7th, 21st and 28th doses with DAS (200 mg/kg) in the chronic experiment. It is likely that the inactivation and inhibition of P450 2E1 by DAS and its metabolites block the oxidation of acetone and cause its elevation in blood. The results strongly suggest an important role of P450 2E1 in acetone catabolism under physiological conditions.

A sensitive and specific high-performance liquid chromatographic (HPLC) method with fluorescence detection was developed for the simultaneous determination of DuP 128 (N'-(2,4-difluorophenyl)-N-[5-(4,5-diphenyl-1H-imidazol-2-ylthio)p entyl]-N- hepthylurea), an ACAT inhibitor, its sulphone metabolite (XB277), and the separate determination of sulphoxide metabolite (XC164) in human plasma. After deproteinizing plasma samples with acetonitrile, the organic layer, created by adding approximately 0.25 g of NaCl, was removed, evaporated to dryness, and the residue then reconstituted with 400 microliters of acetonitrile. The acetonitrile layer was washed with 5 ml of hexane and then 50 microliters was injected into the HPLC. DuP 128 and XB277 were simultaneously quantified using a YMC basic column and fluorescence detection (lambda Ex = 270 nm and lambda Em = 385 nm). XC164 was quantified using a Waters microBondpack C18 reversed-phase column and fluorescence detection (lambda Ex = 270 nm and lambda Em = 365 nm). The relationship between the peak height and plasma concentrations best fit a power curve and showed an average correlation coefficient of > 0.99 over a concentration range of 1-200 ng ml-1 for DuP 128 and XC164 and 2.5-200 ng ml-1 for XB277. Good intraday and interday assay precisions (RSD < 10%) and accuracy (< 14%) for all three compounds were observed. The methods were sufficiently sensitive and selective to quantify plasma concentrations of DuP 128 and its sulphoxide and sulphone metabolites after oral administration of single or multiple dose(s) of > 350 mg of DuP 128 to healthy subjects.

The adsorption of plasminogen, the principal protein of the fibrinolytic pathway in blood, to a number of solid surfaces from plasma was investigated. This study forms part of a larger project to develop a fibrinolytic surface for blood-contacting applications. Polyurethanes incorporating lysine residues were developed in an attempt to promote selective adsorption of plasminogen from plasma through lysine-binding sites in the plasminogen molecule. The adsorption of plasminogen to these surfaces as well as to glass, 'conventional' polyurethanes and precursor sulphonated polyurethanes was investigated. Adsorption from citrated human plasma diluted with isotonic Tris buffer (pH 7.4) was measured under static conditions at room temperature using radioiodinated plasminogen. The following trends were observed. (1) Adsorption increases monotonically with increasing plasma concentration and there is no suggestion of transient adsorption (Vroman effect) on any of the surfaces studied. (2) Sulphonate groups appear to have a strong effect on plasminogen adsorption as was found previously for adsorption from buffer. (3) The lysine-derivatized material having the highest lysine content may show a slight increase in plasminogen binding affinity compared to its sulphonated precursor.