LC—MS法快速测定人血浆中格列吡嗪  

Rapid Determination of Glipizide in Human Plasma and Study of Bioequivalence of Its Tablets in Healthy Subjects

作　　者：伍炜培[1] 谭文明[1] 丁黎[2] 

机构地区：[1]江门市中心医院药剂科,广东江门529030 [2]中国药科大学药物分析教研室,江苏南京210009

出　　处：《国际医药卫生导报》2007年第12期96-100,共5页International Medicine and Health Guidance News

摘　　要：目的 建立快速测定人血浆中格列吡嗪的HPLC-ESI-MS法,测定志愿者口服格列吡嗪片剂10mg后的血药浓度,并对受试制剂和参比制剂的生物等效性进行评价。方法 血浆样品以甲醇沉淀蛋白,直接进行HPLC-ESI-MS分析,色谱柱为LichrospherC18（5μm,250mm×4.6mm）,流动相为10mmol/L乙酸铵缓冲液-甲醇（22：78,V/V）,内标为格列本脲,检测离子分别为m/z444（格列吡嗪）、m/z492（内标）,裂解电压为120V。20名健康志愿者交叉口服供试片和参比片,计算主要药动学参数及相对生物利用度,以判断生物等效性。结果 在10.04～2008ng/ml范围内格列吡嗪与内标的峰面积比值与浓度呈良好的线性关系。受试制剂及参比制剂的消除半衰期分别为（3.46±0.52）小时和（3.56±0.54）小时,达峰时间分别为（2.7±0.7）小时和（2.6±0.8）小时,达峰浓度分别为（734.72±210.34）ng/ml和（743.57±239.77）ng/ml。以AUC0-16计算的受试制剂的相对生物利用度为（96.1%±11.5%）。结论 本实验建立的分析方法快速、灵敏、准确、简便。统计学结果表明两种制剂生物等效。Objective To develop a HPLC-ESI-MS assay for rapid determination of glipizide in human plasma and to investigate the pharmacokinetics and bioequivalence of two glipizide tablets in human.Methods After being deproteined by methanol plasma samples were separated by HPLC on a reversed-phase C18 column with a mobile phase of 10 μmol/L ammonium acetate buffer solution -methanol （22：78, v/v）. HPLC-ESI-MS was performed in the selected ion monitoring （SIM） mode using target ions at m/z 444 for glipizide and m/z 492 for the internal standard. The fragmentor voltage was 120 V. A randomized crossover design was performed in 20 healthy volunteers. In the two study periods, a single 10 mg dose of each tablet was administered to each volunteer. Results Calibration curves were linear over the range 10.04±2008 ng/ml. The limit of quanti fication for glipizide in plasma was 5 ng/ml. The main pharmacokinetic parameter T1/2, Tmax and Cmax were （3.56 ±0.54）h, （2.6±0.8）h and （743.57±239.77）ng/ml for the reference tablet; （3.46 ±0. 52）h, （2.7 ±0. 7）h and （734.72 ±210.34）ng/ml for the test tablet, respectively. The relative bioavalability of the test tablet was （96.1%± 11. 5%）. The results of variance analysis and two one-sided t-test showed that there was no significant difference between the two formulations in the AUC and Cmax. Conclusion The assay was proved to be rapid, sensitive, accurate and convenient. The two formulations were bioequivalent.

关 键 词：格列吡嗪 LC—ESI—MS 快速分析 药代动力学 生物等效性 

分 类 号：O[理学] R9[医药卫生—药学]