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

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 (r(2) = 0.9967) 30 to 10,000 ng/mL for ticarcillin S (r(2) = 0.9961), and 30 to 10,000 ng/mL for clavulanate (r(2) = 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.