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Glucose tetrasaccharide (Glc4) and maltotetraose (M4) are important biomarkers for Pompe disease and other glycogen storage diseases (GSDs). With the development of new treatments for GSDs, more specific and sensitive bioanalytical methods are needed to determine biomarkers. In recent years, differential mobility spectrometry (DMS) has become an effective analytical technique with high selectivity and specificity. This study aimed to develop an efficient analytical method for the two urinary tetrasaccharide metabolites using DMS and apply it to patients with GSDs (type Ib and II). Urine samples were directly diluted and injected into liquid chromatography-differential mobility spectrometry tandem mass spectrometry (LC-DMS-MS/MS). Chromatographic separation was performed on an Acquity™ UPLC BEH Amide column (2.1 × 50 mm, 1.7 μm) with a short gradient elution of 2.6 min. DMS-MS/MS was used to detect two urinary tetrasaccharide metabolites in a negative multiple reaction monitoring mode with isopropanol as a modifier. A total of 20 urine samples from 6 healthy volunteers and 10 patients with GSDs (type Ib and II) were collected for analysis. The method was linear over a concentration range of 0.5~100.0 µg/mL for each urinary tetrasaccharide (r≥0.99). The intra- and inter-day precision RSD% were less than 14.3%, and the accuracy RE% were in the range of −14.3~13.4%. The relative matrix effect was between 86.6 and 114.3%. No carryover or interference was observed. Patients with GSDs (type Ib and II) had significantly higher median urinary Glc4 (P=0.001) and M4 (P=0.012) excretion than healthy subjects. The developed method was simple, rapid, sensitive, and specific. It was successfully applied to healthy volunteers and patients with GSDs (type Ib and II). DMS technology greatly improved analysis efficiency and provided high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Objective: Primary aldosteronism (PA) is a common form of secondary hypertension. Adrenal venous sampling (AVS) is the gold standard for subtyping PA. This study aimed to determine whether there is a difference between immunoassays and liquid chromatography‐mass spectrometry (LC‐MS/MS) methods for measuring cortisol levels that affect the judgement of AVS. Design: This was a retrospective study. Patients: Included 72 patients who were diagnosed with PA and had undergone AVS. Measurements: Patients were grouped according to whether they received adrenocorticotropic hormone (ACTH) stimulation during AVS, and the cortisol results were measured using immunoassay and LC‐MS/MS. Results: There were 48 patients in the without ACTH stimulation group and 24 in the post‐ACTH stimulation group during AVS (bilateral adrenal vein cannulation success rate, 56.25% vs. 83.33%). ACTH stimulation was beneficial for increasing the success rate of AVS (p <.001). Immunoassays were linearly correlated with LC‐MS/MS when cortisol concentrations were <1750 nmol/L (r =.959, p <.001). When cortisol concentrations were >17,500 nmol/L, no correlation was found between the two methods (p =.093). The two methods were consistent for the detection of cortisol for evaluating the success of cannulation for AVS. Five percent of patients showed discordant lateralization of aldosterone production according to the cortisol LC‐MS/MS and immunoassay results in the without ACTH group, and 15% showed discordant lateralization in the post‐ACTH group. Conclusions: The immunoassay method can be used to determine whether cannulation is successful. The final decision for lateralization may be more appropriate based on LC‐MS/MS results. [ABSTRACT FROM AUTHOR]

Objective: We investigated the relationship between fasting serum fructose levels and the risk of incident type 2 diabetes in a prospective Chinese cohort.Research Design and Methods: Among 949 community-based participants aged ≥40 years without diabetes at baseline, fasting serum fructose levels were measured using liquid chromatography-tandem mass spectrometry. The participants were followed up for the occurrence of diabetes. Cox regression models were performed to analyze the effect of fasting serum fructose levels on risk of incident diabetes.Results: During a median of 3.5 years' follow-up, 179 of 949 (18.9%) participants developed type 2 diabetes. Elevated fasting serum fructose levels were associated with an increased risk of incident diabetes in a dose-response manner. After adjustment for age, sex, BMI, lipid profiles, blood pressure, liver function, smoking and drinking status, baseline glucose level, and sugar-sweetened beverage consumption, a 1-SD increased fasting fructose level was associated with a 35% (95% CI 1.08-1.67) increased risk of developing diabetes. After further adjustment for serum uric acid and estimated glomerular filtration rate, the association was partially attenuated (hazard ratio 1.33 [95% CI 1.07-1.65]). The association was similar by age, prediabetes status, BMI, and family history of diabetes but attenuated in women (P for heterogeneity = 0.037).Conclusions: Elevated fasting serum fructose levels were independently associated with increased risk of incident type 2 diabetes in a middle-aged and older Chinese population. Our data suggest that higher fasting serum fructose levels might serve as a biomarker and/or a contributor to incident diabetes. [ABSTRACT FROM AUTHOR]

Objective. The aim of the study was to investigate the independent and combined effects of the cortisol-to-cortisone ratio (F/E) and 11-deoxycortisol on prediabetes and type 2 diabetes mellitus (T2DM) among different genders. Methods. A case-control study was performed including 2676 participants from the Henan Rural Cohort Study. Liquid chromatography-tandem mass spectrometry was used to assess serum cortisol, cortisone, and 11-deoxycortisol. Conditional logistic regression was performed to estimate the associations between hormones and outcomes. Results. After adjusting for multiple variables, the negative associations of F/E and 11-dexyocortisol with T2DM were observed in females (T3 vs. T1: OR=0.56, 95% CI: 0.39-0.80 for F/E; T3 vs. T1: OR=0.44, 95% CI: 0.27-0.73 for 11-dexyocortisol). However, only 11-dexyocortisol showed a negative association with prediabetes both in males and females. Compared with the combination of low F/E and 11-dexyocortisol, the combination of middle F/E and high 11-dexyocortisol was significantly associated with prediabetes (OR=0.29, 95% CI: 0.12-0.71) in males. Furthermore, the combination of high F/E and 11-dexyocortisol was associated with the lowest odds of prediabetes (OR=0.39, 95% CI: 0.21-0.73) and T2DM (OR=0.25, 95% CI: 0.12-0.52) in females. Conclusions. Serum F/E level was negatively associated with T2DM only in females whereas serum 11-deoxycortisol level was negatively associated with prediabetes in males and with prediabetes and T2DM in females. Additionally, their combination has a synergistic effect on T2DM. [ABSTRACT FROM AUTHOR]

Aims: We aimed to investigate the association of serum testosterone with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) and calculate the proportion explained by obesity status on the relationship.Materials and Methods: A case-control study including 2775 participants was performed. Serum testosterone was quantified by liquid chromatography-tandem mass spectrometry. Conditional logistic regression and multivariable linear regression were performed to estimate the relationships between testosterone and different glucose status. Waist circumference (WC) was used as a mediator to estimate the mediation effect.Results: After adjusting for multiple variables, serum testosterone levels were negatively associated with T2DM in males (per 1 unit natural log-transformed, odd ratio (OR) = 0.73, 95% confidence interval (CI): 0.56, 0.96; Tertile 3 vs Tertile 1, OR = 0.46, 95% CI:0.29, 0.72) while were positively in females (per 1 unit natural log-transformed, OR = 1.56, 95% CI:1.32, 1.84; Tertile 3 vs Tertile 1, OR = 3.55, 95% CI: 2.22, 5.66). In males, a higher testosterone tended to be associated with a lower fasting plasma glucose level and a weaker HOMA2-IR but a stronger HOMA2-β. Opposite findings were observed in females. Furthermore, WC played a full and partial mediating role in the relationship between testosterone and IFG and T2DM both in males and females.Conclusion: Serum testosterone levels had opposite effects on IFG and T2DM in males and females. With higher serum testosterone levels, the dysglycemia progression was decreased among males while increased among females. In addition, WC played a full and partial mediating role in the relationship between testosterone and IFG and T2DM. [ABSTRACT FROM AUTHOR]

• A global method determines four anti-TB drugs in various biological milieus. • Two-dimensional column-switch arrangement improves the method performance. • The extraction methods of tissues and feces are optimized. • Extra-liver tissue samples are calculated by liver curves. • Co-administration of anti-TB drugs enlarges the plasma exposures of protionamide. A novel and potent anti-tuberculosis drug combination pyrazinamide (PZA), ethambutol (EMB), protionamide (PTO), and clofazimine (CFZ) that rapidly kills Mycobacterium tuberculosis (Mtb) in the lungs has been identified using the artificial-intelligence-enabled parabolic response surface approach. A universal and highly sensitive two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) method for the simultaneous determination of PZA, EMB, PTO, and CFZ in various biological samples in different states (liquid samples: plasma, bile, and urine; solid samples: tissue and feces) using simple pretreatment was established and validated. For the first dimension of this column-switching arrangement, the automated purification and enrichment of the drugs were achieved on a Polar-RP column. The subsequent analytical separation was performed on an Agilent Zorbax SB-Aq column, and the total loop time was 7.5 min. The positive-ionization mode with multiple reaction monitoring was used for detection. The sensitivity was good with no carry-over detected, and the lower limit of quantification ranged from 100 to 500 pg/mL. This quantification method was fully validated and proved to be robust in accordance with US Food and Drug Administration guidelines. High recoveries (85.3–111.4%) and accuracies (92.1–109.3%), together with high precision values (0.5–13.8%), were verified in all matrices. All standard curves showed favorable linearities with r 2 > 0.995. This validated method was applied to study plasma pharmacokinetics, tissue distribution, and excretion in Sprague–Dawley rats after oral administration of the drug combination. [ABSTRACT FROM AUTHOR]

• A reliable analytical method was developed for urinary saccharide metabolites. • It provides support for exploring the potential of maltotetraose as a biomarker for Pompe disease. • It is meaningful to monitor disease progression and determine treatment response. • The method is simple, convenient and easy to promote. Urinary 1,5-anhydroglucitol (1, 5-AG), 6-α-D-glucopyranosyl-maltotriose (Glc 4) and maltotetraose (M 4) are important biomarkers for glycogen storage disease (types Ib and Ⅱ). This study aimed to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to detect these three urinary saccharide metabolites. Urine samples were diluted and then analyzed. Chromatographic separation was performed on an Acquity™ UPLC Amide column (2.1 × 100 mm, 1.7 μm) with gradient elution. The quantitation of analytes was achieved on a 5500 Qtrap mass spectrometer using negative multiple reaction monitoring (MRM) mode. The calibration curves for all analytes were linear over the range of 0.500 to 100 μg/mL with a correlation coefficient, R2 ≥ 0.999. The percent relative standard deviations (RSD%) were ≤12.8%, and the percent relative errors (RE%) were in the range of −11.7%–11.0%. The relative matrix effects of all analytes were between 87.2% and 104% with RSD% < 3.10% across three concentrations. The developed analytical method was simple, accurate, and reliable for rapid and simultaneous analysis of these three urinary saccharide metabolites. It was applied to healthy volunteers and patients. To our knowledge, it was the first validated assay for urinary maltotetraose quantification. This work provides support for exploring the potential of maltotetraose as a biomarker for Pompe disease. [ABSTRACT FROM AUTHOR]

• A simple bioanalytical method was first established and validated for CBMIDA. • Direct determination of the chelator itself instead of metal complex. • Improved peek shape was achieved by pulse gradient method. • Poor accuracy and linearity were overcome by addition of EDTA in the mobile phase. • Successful application to pharmacokinetic study. It is usually somewhat difficult to analyze the metal chelators, especially in complex biological matrix, because of the interference of metal ions in both the matrix and analyzing system. In this study, an innovative and simple bioanalytical method was established and validated for the quantification of a newly developed uranium chelator catechol-3, 6-bis (methyleiminodiacetic acid) (CBMIDA) in beagle dog plasma. Different analytical columns and mobile phase were tested for effective chromatography resolution and sensitive and reproducible response of CBMIDA and the internal standard. An Agilent Zorbax SB AQ column was chosen. Excessive peak tailing, peak asymmetry, low recovery, and poor reproducibility, which are generally observed in chromatographic analysis of metal chelators, were overcome by the use of a pulse gradient method and addition of ethylene diamine tetraacetic acid (EDTA) to the mobile phase at 8 μg mL−1, enabling good peak shape, low matrix interference, high precision and good linearity for CBMIDA quantification in beagle dog plasma. Plasma sample pretreatment was performed by a simple, high throughput protein precipitation step with 2.5 mM EDTA methanol solution in a 96-well protein precipitation plate without complexing with the metal ions, and the sample was directly analyzed by electrospray ionization mass spectrometry. By shifting the analysis target from the metal complex to metal chelator itself, the method has an advantage over the existing method for determination of EDTA and diethylenetriaminepentaacetic acid owing to increased sample throughput and apparent simplicity. The assay was validated in accordance with the United States Food and Drug Administration guidelines and successfully applied to the pharmacokinetic study of CBMIDA in beagles after intramuscular injection of CBMIDA at different doses. The method was sensitive enough for the detection of CBMIDA concentration at 4 elimination half-times. The experimental strategies presented herein may be helpful for the measurement of other radionuclide chelators in biological matrices. [ABSTRACT FROM AUTHOR]