HPLC-MS/MS测定人血浆中羧甲司坦的浓度及其生物等效性研究

目的 建立HPLC-MS/MS方法测定人血浆中的羧甲司坦体内浓度,用于人体生物等效性分析.方法 以直接沉淀法处理血浆,色谱柱为XTerra MS C18柱(150 mm×2.1mm,5μm)；流动相为甲醇-20 mmol,L-1甲酸铵(含0.5％甲酸)(75∶25,v/v)；流速为0.3 mL· min-1；柱温为40℃.采用电喷雾离子源(ESI)负离子模式,用多反应监测模式(MRM)进行定量分析.结果 羧甲司坦线性范围为0.210 9～54 μg,mL-1,定量下限为0.210 9 μg·mL-1,绝对回收率＞80％,日内和日间RSD均＜15％.结论 此方法能够简便、高效、快速和灵敏的检测健康志愿者血浆中的羧甲司坦,可用于羧甲司坦药物代谢动力学及生物等效性研究.

HPLC-MS/MS method for the determination of carbocisteine in human plasma and its bioequivalence

Objective To establish a liquid chromatography-electrospray ionization tandem mass spectrum(HPLC-ESI-MS/MS) method to determine the carbocisteine in human plasma.Methods The XTerra MS C18(150 mm×2.1 mm,5 μm) column was used.The mobile phase was composed of 20 mmol·L-1 ammonium formate with 0.5% formic acid-methanol(25∶75,v/v),the flow rate was 0.3 mL·min-1,and the column temperature was 40 ℃.The ionization was optimized with ESI(-) and selectivity was enhanced with tandem mass spectrometric analysis via MRM functions,m/z 178.0→90.9 for carbocisteine and m/z 122→78.0 for the internal standard.Results The calibration curve was linear at 0.210 9-54 μg·mL-1(r= 0.998)for arbocisteine.The absolute recovery was more than 80%.The inter-day and intra-day RSDs were all less than 15%.Conclusion The method is simple,rapid,efficient,sensitive and suitable for the content determination of carbocisteine in the plasma of healthy volunteers,which can be used in the pharmacokinetics and bioequivalence research of carbocisteine.