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目的:建立HPLC-MS测定人血浆中格列吡嗪的方法,并研究其在健康人体内的药动学特征。方法:以格列本脲为内标,血样经乙酸乙酯提取,采用Lichrospher ODS(250mm×4.6mm,5μm),以甲醇-10mmol·L~(-1)醋酸铵水溶液(80:20)为流动相,流速1.0ml·min~1;质谱选择性检测阴离子质荷比(m/z)444.2。24名健康受试者随机分成两组,分别进行高、中、低剂量和中剂量多次给药药物动力学试验。结果:格列吡嗪的线性范围为3.0～2000ng·ml~(-1)(r=0.9995,n=5),提取回收率>92%,日内和日间RSD均≤11.1%。格列吡嗪的t_(1/2)为3.64h～3.90h,MRT为5.62h～5.91h;多次给药后pss-min为(85.20±18.98)ng·ml~(-1),DF为(2.01±0.36),R为(0.91±0.10)。结论:该法灵敏、准确、简便。在本研究剂量范围内,格列吡嗪呈线性动力学特征且在健康受试者体内不存在累积现象。
OBJECTIVE: To establish a HPLC-MS method for the determination of glipizide in human plasma and study its pharmacokinetics in healthy volunteers. Methods: Glibenclamide was used as internal standard. The blood samples were extracted with ethyl acetate. Lichrospher ODS (250mm × 4.6mm, 5μm) was used in this study. The aqueous solution of methanol - 10mmol·L -1 ammonium acetate (80:20) was Mobile phase, the flow rate of 1.0ml · min ~ 1; mass selective detection of anion mass to charge ratio (m / z) 444.2.24 healthy subjects were randomly divided into two groups, respectively, high, medium and low dose and medium dose multiple Administration of pharmacokinetic test. Results: The linear range of glipizide was 3.0-2000ng · ml -1 (r = 0.9995, n = 5). The extraction recovery was> 92%. The intra-day and interday RSD were all ≤11.1%. The t_ (1/2) of glipizide was 3.64h ~ 3.90h and the MRT was 5.62h ~ 5.91h. The pss-min was (85.20 ± 18.98) ng · ml ~ (2.01 ± 0.36), R was (0.91 ± 0.10). Conclusion: The method is sensitive, accurate and easy. Glipizide was linearly kinetic in the dose range studied and there was no accumulation in healthy subjects.