Validation of an LC-MS/MS method for quantitation of fostemsavir in plasma.

BACKGROUND: A novel, sensitive and specific LC-MS/MS technique was developed and validated for the quantification of fostemsavir in human plasma and its pharmacokinetic application in rabbits. METHODS: Chromatographic separation of the fostemsavir and fosamprenavir (internal standard) were achieved on Zorbax C18 (50 mm × 2 mm × 5 µm) column with 0.80 mL/min flow rate and coupled with API6000 triple quadrupole MS in multi reaction monitoring mode by applying mass transitions m/z 584.16/105.03 for fostemsavir and m/z 586.19/57.07 for the internal standard. RESULTS: The calibration curve exhibited linearity in concentration range of 58.5-2340.0 ng/mL for fostemsavir. The LLOQ was 58.5 ng/mL. The validated LC-MS/MS process was effectively applied for the analysis of plasma in healthy rabbits for determinations of Fostemsavir. From the pharmacokinetic data, the mean of Cmax and Tmax were 198.19 ± 5.85 ng/mL and 2.42 ± 0.13, respectively. Plasma concentration reduced with t1/2 of 7.02 ± 0.14. AUC0→Last value obtained was 2374.87 ± 29.75 ng. h/ml, respectively. CONCLUSION: In summary, the developed method has been successfully validated and pharmacokinetic parameters were demonstrated after oral administration of Fostemsavir to healthy rabbits.

The simultaneous quantification of Sitagliptin and Irbesartan in rat plasma using the validated LC-MS/MS method is applied to a pharmacokinetic study.

Irbesartan (IRB), an angiotensin II receptor AT1 blocker, is an antihypertensive agent commonly used with Sitagliptin (STG), a novel antidiabetic agent in diabetes. A finalised and validated LC-MS/MS method was used for the bioanalytical quantification of STG and IRB to be applicable to studies on the P.K drug-drug interactions between STG and IRB. Using a YMC triart C18 column (50 mm × 4.6 mm i.d., 3 µm), both the drugs and the Tolbutamide were separated using a gradient mode with a flow rate of 1 ml/min with run time of 5 min. For analyte detection, an LC-MS/MS system with multiple reaction monitoring (MRM) was used. The technique was validated across a concentration range of 5-1000 ng/ml, with the LLOQ for both analytes being 5 ng/ml. At all QC levels accuracies from spiked samples were > 83% for both drugs and internal standards. The accuracy for STG within-batch and between-batch was found within 98.4-107.2%, and for IRB was found within 92.4-102.5%. The precision for STG within batch and between batches was less than 12.3% CV, and for IRB was less than 10.2% CV at all concentration levels. The pharmacokinetic profiles of STG and IRB were successfully applied on simultaneous oral administration to rats. This method applies to pharmacokinetic multidrug interaction studies.