高效液相-质谱法测定人血浆中乐卡地平的浓度

Quantification of lercanidipine in human plasma by HPLC-MS

目的:建立测定人血浆中乐卡地平浓度的高效液相-质谱(HPLC-MS)方法。方法:血浆中加入内标贝尼地平,经正己烷与异丙醇混合液(体积比100∶1)提取后,利用HPLC-MS法测定血浆中乐卡地平的浓度。本实验测定了19名志愿者单剂量交叉口服乐卡地平试验制剂与参比制剂后的血药浓度的经时过程。结果:乐卡地平在0.2～10μg.L-1范围内线性关系良好,最低检测限为0.1μg.L-1,定量限为0.2μg.L-1,方法回收率大于80%,日内、日间的精密度均小于9.7%。结论:本方法灵敏度高,准确性好,能满足乐卡地平治疗药物的临床监测要求,并适用于乐卡地平药动学和生物利用度的研究。

OBJECTIVE To establish a determination method for lercanidipine in human plasma by high-performance liquid chromatography mass spectrometry （HPLC-MS）. METHODS The human plasma added internal standard benidipine was extracted by hexane/isopropanol （100： 1, v/v）, subsequently, the extraction was determined by HPLC-MS. LC-ESI MS teas used in the selected positive ion monitoring（SIM） mode. In this assay, concentrations of lercanidipine in plasma of 19 volunteers after oral administration of lercandipine hydrochloride testand reference tablets were determined. RESULTS The assay quantifies over a linear range of 0. 2μg· L^-1 to 10μg· L^-1 with a minimum detectable limit of 0. 1 μg· L^-1 at a signal/noise ratio of 3, and the limit of quantification was 0. 2μg· L^-1. The recovery of the method was more than 80%. The intra-assay RSD （same-day） and the inter-assay RSD （different day） were lower than 9. 7%. CONCLUSION The determination method for lercanidipine in human plasma by HPLC-MS described in this paper is sensitive, accurate and suitable for quantitative determination and pharmacokinetics and bioavailability study of lercanidipine.