LC／MS／MS法测定人血中硫普罗宁的浓度及药物动力学研究

目的建立LC／MS／MS法测定人血中硫普罗宁浓度的方法，并研究其在健康男性受试者体内的药物动力学。方法采用LC／MS／MS（ESI源）测定硫普罗宁的血浆浓度，计算药物动力学参数。结果硫普罗宁线性范围为25．0-5000ng·mL^-1，定量下限为25．0ng·mL^-1日内、日间精密度（RSD）均〈15％，准确度（RE）在15％以内。应用本法测得20名健康男性受试者口服200mg硫普罗宁胶囊后主要药代动力学参数为：tmax，为（4．20±1．01）h，t1／2为（5．61±4．42）h，Cmax为（4456±2447）ng·mL^-1，AU C0-24h为（20566±9902）ng·mL^-1,Ke为（0．173±0．094）h^-1。结论该法操作简便、快速、灵敏，可用于测定血浆中硫普罗宁浓度。

Determination of tiopronin in human plasma by LC/MS/MS and its pharmacokinetics

Objective To develop an LC/MS/MS method to determine tiopronin in human plasma and to study its pharmacokinetics in healthy male volunteers. Methods The concentrations of tiopronin were determined by LC/MS/MS with ESI and the pharmacokinetic parameters were calculated. Results The linear calibration curve was obtained at 25.0-5 000 ng·mL^-1 for tiopronin . The lower limit of quantiation was 25.0 ng·mL^-1. The intra-day and interday precision （RSD） was less than ±15%, and the accuracy （relative error） was within ±15%. The pharmacokinetie parametes were as follows： tmax was （4.20±1.01） h, t1/2 was （5.61±4. 42） h, Cmax was（4 456±2 447）ng·mL^-1, AUC0-24h was （20 566±69 902） ng·mL^-1, and Ke was （0.173±0. 094） h^-1. Conclusion The method is suitable for clinical investigation of tiopronin, which is convenient, sensitive and specific.