A selective, sensitive and fast LC-MS/MS method for cabotegravir quantification in rat plasma and pharmacokinetic investigations.

ABSTRACT

This study presents a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying cabotegravir (CAB) in rat plasma. A novel, sensitive, and rapid LC-MS/MS method has been developed and validated. Furthermore, protein precipitation technique allowed us to lowered the limit of quantification (LOQ) to nanogram levels, allowing detection of smaller CAB amounts in plasma samples. A review of scientific literature reveals that this method is superior than published methods in terms of runtime, sensitivity, wide linearity, and cost, using LC-MS/MS to quantify CAB in biological samples. CAB reached its maximum concentration (Cmax) of 78.401 µg/mL in rat plasma at 1.50 h (Tmax). Linearity was evaluated across 0.05-1000 µg/mL for CAB using five calibration curves with at least nine standards each with r2 > 0.9997. The intra- and inter-day precision and accuracy results were below 15% and acceptable as per Food and Drug Administration (FDA) guidelines. Stability of compounds were established in a battery of stability studies, that is, benchtop, autosampler, and long-term storage stability as well as freeze thaw cycles. The validated method can be used as a routine method to support pharmacokinetic studies.