Determination and pharmacokinetic analysis of ticarcillin disodium–clavulanate potassium for injection in rat plasma by UPLC-ESI-MS/MS

Abstract

Objective To establish a specific and rapid ultra-high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC-ESI-MS/MS) method for measuring ticarcillin and clavulanate levels in rat plasma. Methods A Waters ACQUITY BEH C18 column (50 mm × 2.1 mm, 1.7 μm) and SCIEX QTRAP® LC-MS/MS System were used. Analyses were conducted to optimize the chromatographic and MS conditions, and the pharmacokinetic parameters of ticarcillin and clavulanate were assessed. Results Linear relationships were observed in the ranges of 10 to 10,000 ng/mL for ticarcillin R (r2 = 0.9967) 30 to 10,000 ng/mL for ticarcillin S (r2 = 0.9961), and 30 to 10,000 ng/mL for clavulanate (r2 = 0.9981). The average extraction recoveries of all compounds ranged from 86.9% to 96.4%. The pharmacokinetic parameters of the ticarcillin R and S isomers in rats were distinctive. The ticarcillin R and S isomers and clavulanate were rapidly absorbed in vivo. Ticarcillin S and clavulanate had similar elimination rates, whereas that of ticarcillin R was slower. Conclusion A UPLC-ESI-MS/MS method was developed and validated for the determination of ticarcillin and clavulanate in rat plasma.