超高效液相色谱-电喷雾串联质谱法测定大鼠血浆中注射用替卡西林钠-克拉维酸钾并进行药代动力学分析
Determination and pharmacokinetic analysis of ticarcillin disodium-clavulanate potassium for injection in rat plasma by UPLC-ESI-MS/MS.
作者信息
Wang Moli, Gao Yanxia, Liu Xueli, Zhang Jing, Wang Qiang, Chang Junshan, Zhang Lantong
机构信息
Department of Pharmaceutical of Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, China.
Department of Chemical Drug Control, Hebei Institute of Drug Control and Research, Shijiazhuang, China.
出版信息
J Int Med Res. 2020 Dec;48(12):300060520967822. doi: 10.1177/0300060520967822.
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 = 0.9967) 30 to 10,000 ng/mL for ticarcillin S (r = 0.9961), and 30 to 10,000 ng/mL for clavulanate (r = 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 . 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.
目的
建立一种特异、快速的超高效液相色谱-电喷雾电离-串联质谱法（UPLC-ESI-MS/MS），用于测定大鼠血浆中替卡西林和克拉维酸的含量。
方法
采用沃特世ACQUITY BEH C18柱（50 mm × 2.1 mm，1.7 μm）和SCIEX QTRAP® LC-MS/MS系统。进行分析以优化色谱和质谱条件，并评估替卡西林和克拉维酸的药代动力学参数。
结果
替卡西林R在10至10,000 ng/mL范围内呈线性关系（r = 0.9967），替卡西林S在30至10,000 ng/mL范围内呈线性关系（r = 0.9961），克拉维酸在30至10,000 ng/mL范围内呈线性关系（r = 0.9981）。所有化合物的平均提取回收率在86.9%至96.4%之间。大鼠体内替卡西林R和S异构体的药代动力学参数不同。替卡西林R和S异构体以及克拉维酸吸收迅速。替卡西林S和克拉维酸的消除速率相似，而替卡西林R的消除速率较慢。
结论
建立并验证了一种UPLC-ESI-MS/MS方法，用于测定大鼠血浆中替卡西林和克拉维酸的含量。
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