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Background and Purpose: The study was aimed at validating a simple, rapid, and low-cost LC-MS/MS method for carvedilol and 4 / -hydroxyphenyl carvedilol assay in human plasma. The validated method was applied to investigate the pharmacokinetics after a low dose of 6.25 mg. carvedilol., Experimental Approach: In this study, the plasma was extracted by liquid-liquid extraction and evaporated the organic layer to dryness, then both analytes in the residue were reconstituted and detected by LC- MS/MS. The method was validated following the guideline on bioanalytical method validation. Thirty-one healthy volunteers participated in the pharmacokinetic study. After 10 h of fasting, each volunteer received one tablet of 6.25 mg carvedilol orally. Blood samples were collected at 16 prescheduled time points. The plasma samples were analyzed for pharmacokinetics., Findings/results: The method was linear over a range of 0.050-50.049 ng/mL for carvedilol and 0.050- 10.017 ng/mL for 4 / -hydroxyphenyl carvedilol. Crucial validated results reached the requirements of selectivity, accuracy, precision, and stability. Pharmacokinetics of carvedilol and 4 / -hydroxyphenyl carvedilol were evaluated which showed C max at 21.26 ± 9.23 and 2.42 ± 2.07 ng/mL; AUC0-t 66.95 ± 29.45 and 5.93 ± 3.51 ng.h/mL; AUC 0-inf 68.54 ± 30.11 and 6.78 ± 3.49 ng.h/mL; and T1/2 6.30 ± 1.95 and 6.31 ± 6.45 h, respectively., Conclusion and Implications: The validated method was able to detect and quantify both analytes in plasma samples and can be applied to the pharmacokinetic study of carvedilol and 4 / -hydroxyphenyl carvedilol after receiving carvedilol at 6.25 mg orally., Competing Interests: The authors declared no conflicts of interest in this study., (Copyright: © 2022 Research in Pharmaceutical Sciences.)

Objective: The purpose of the study was to evaluate the pharmacokinetics and bioequivalence of pregabalin following administration of a 150-mg capsule of test and reference products., Method: The study was designed as a randomized, two-treatment, two-period, two-sequence, single-dose crossover with 1-week washout period between period I and period II dosing. 20 healthy male and female Thai subjects were enrolled in the study. Each subject was in fasted state for ~ 10 hours prior to receiving a single oral 150-mg pregabalin capsule. Serial blood samples were collected at pre-dose until 32 hours after drug administration. Plasma samples were extracted by protein precipitation and derivatized with 4-chloro-7-nitrobenzofurazan. Pregabalin plasma concentrations were determined by HPLC method, and pharmacokinetic parameters were calculated. For bioequivalence assessment, the differences of C max , AUC 0-t , and AUC 0-inf means based on ln-transformed data were assessed by the 90% confidence interval (CI)., Results: Pharmacokinetic parameters were determined that test and reference products showed 0.96 ± 0.35 and 1.04 ± 0.96 hours for t max , 4,594.217 ± 834.195 and 4,568.68 ± 573.963 ng/mL for C max , 30,048.150 ± 2,998.920 and 29,315.722 ± 2,747.396 ng×h/mL for AUC 0-t , 30,594.210 ± 2,872.317 and 29,831.454 ± 2,688.020 ng×h/mL for AUC 0-inf , respectively. The 90% CIs of C max , AUC 0-t , and AUC 0-inf for test and reference products were assessed at 95.356 - 104.630%, 99.303 - 105.751%, and 99.373 - 105.788%, respectively. The results were within the acceptance criteria of 80 - 125%., Conclusion: Pharmacokinetic parameters of a single oral 150-mg pregabalin capsule in healthy Thai subjects were evaluated and showed rapid absorption. 90% CI for the differences of C max , AUC 0-t , and AUC 0-inf were within the acceptable range of the criteria so that bioequivalence of the test and reference products of pregabalin 150-mg capsule could be concluded.
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