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

Abstract

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 C_max and T_max were 198.19 ± 5.85 ng/mL and 2.42 ± 0.13, respectively. Plasma concentration reduced with t_1/2 of 7.02 ± 0.14. AUC_0→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.

Keywords: Fostemsavir; HIV/AIDS; LC-MS/MS; Pharmacokinetics; Rabbits; Validation.