固相萃取HPLC-MS(TOF)法测定人血浆中雷米普利拉的浓度

HPLC-MS(TOF)determination of ramiprilat in human plasma by solid-phase extraction

目的:建立测定人血浆中雷米普利拉的 HPLC-MS(TOF)法。方法:以喹那普利为内标,血浆样品经固相萃取小柱提取后,采用 HPLC-MS(TOF)联用技术,以电喷雾(ESI)作为接口技术,选择雷米普利拉的准分子离子([M+H]^+,m/z 389)和内标喹那普利的准分子离子([M+H]^+,m/z 439)作为测定离子,测定人血浆中雷米普利拉的浓度。结果:雷米普利拉的线性范围为0.5～40ng·mL^(-1),日内精密度与日间精密度均小于10%。结论:该测定方法具有灵敏、专一和快速的优点,可满足雷米普利在人体内药代动力学研究的要求。

Objective： To establish a sensitive and specific liquid chromatography - mass spectrometry （ time - of - fly） [ LC -MS（TOF） ] method for the determination of ramipfilat in human plasma. Method： Ramipfilat and the internal standard quinapfil were extracted from the human plasma using SPE column, then separated on a Symmetry C18 column. The mobile phase consisted of methanol - acetic acid（47：53 ,v/v） ,and was set at a flow rate of 0. 3 mL ·min^- 1. Detection is performed on a time - of - flight mass spectrometer equipped with an ESI interface and operated in positive - ionization mode. Ramipfilat quantity was realized by computing the peak area ratio （ ramiprilat m/z 389/quinapfil m/z 439 ） and comparing them with calibration curve （ r = 0. 9995 ）. Results： The linear calibration curve was obtained in the concentration range of 0. 5 -40 ng · mL^-1. The low limit of quantitative was 0. 5 ng · mL^-1. Within -day and between -day precisions were less than 10%. Conclusion ：The method is sensitive, simple and rapid for drug level monitoing in clinical pharmacokinetics study.