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目的:建立人血浆中米格列奈浓度的高效液相色谱-质谱(HPLC-MS)测定法,研究米格列奈钙片在中国健康志愿者体内的药动学。方法:血浆样品中加入内标那格列奈后,上Strata-X固相萃取柱,以60%乙腈溶液洗脱。色谱柱为ThermoC18色谱柱,流动相为乙腈-0.1%甲酸溶液(60∶40),流速为1mL.min-1,1/4分流进入色谱柱,HPLC-MS/ESI+法选择性监测准分子离子峰[M+H]+(米格列奈:m/z=316,内标:m/z=318)。30名健康志愿者随机分为3组,每组10人,男女各半,分别单剂量口服米格列奈钙片5,10和20mg后,在设计的时间点取静脉血,用建立的方法测定血药浓度,药动学参数采用3P97程序计算。结果:米格列奈在10.0~6 000.0mg.L-1内线性关系良好,r=0.998 2,萃取回收率大于86.0%,方法回收率为97.2%~106.8%,日内、日间RSD均小于8.1%。单剂量口服米格列奈钙片5,10,20mg后,主要药动学参数tmax分别为:(0.37±0.15)、(0.32±0.17)和(0.37±0.17)h,Cmax分别为:(716.9±209.2)、(1 857.8±530.2)和(3 551.9±929.1)mg.L-1,AUC0-8分别为:(1 071.7±337.2)、(2 224.2±707.6)和(5 096.7±1 005.6)mg.h.L-1,AUC0-∞分别为:(1 151.0±386.2)、(2 283.7±741.7)和(5 210.8±1 006.8)mg.h.L-1,t1/2分别为:(1.83±0.29)、(1.79±0.29)和(1.6±0.3)h,V/F分别为:(12.9±5.8)、(12.2±4.0)和(9.2±2.7)L,CL/F分别为:(4.7±1.4)、(4.8±1.6)和(4.0±0.7)L.h-1,MRT0-8分别为:(2.5±0.4)、(2.00±0.28)和(2.14±0.24)h。结论:HPLC-MS方法可用于米格列奈钙片在人体内的药动学研究。中国健康志愿者单剂量口服米格列奈后血药浓度-时间曲线符合一级药动学过程。
Objective: To establish a high performance liquid chromatography-mass spectrometry (HPLC-MS) method for the determination of mitiglinide in human plasma and study the pharmacokinetics of mitiglinid in Chinese healthy volunteers. METHODS: Plasma samples were spiked with an internal standard of nateglinide and then applied to Strata-X SPE cartridges eluted with 60% acetonitrile. The column was ThermoC18 column, the mobile phase was acetonitrile-0.1% formic acid solution (60:40), the flow rate was 1mL.min-1, and the flow was split into the column. The HPLC-MS / ESI + Peak [M + H] + (mitiglinide: m / z = 316, internal standard: m / z = 318). Thirty healthy volunteers were randomly divided into three groups of 10 men and women in each half, respectively, after a single oral dose of 5,10 and 20 mg of mitochondrial calcium tablets, at the design time point to take venous blood, with the established method Determination of plasma concentration, pharmacokinetic parameters using 3P97 program. Results: The linear relationship of mitiglinide in 10.0-6 000.0mg.L-1 was good, r = 0.998 2, the recovery rate was more than 86.0%, and the recovery rate was 97.2% -106.8%. The intra-day and interday RSDs were less than 8.1%. The main pharmacokinetic parameters tmax were (0.37 ± 0.15), (0.32 ± 0.17) and (0.37 ± 0.17) h, respectively, after a single dose of 5,10,20 mg of mitochondrial calcium was administered. The Cmax values were (716.9 Respectively, and the AUC0-8 were (1 071.7 ± 337.2), (2 224.2 ± 707.6) and (5 096.7 ± 1 005.6), respectively (1 151.0 ± 386.2), (2 283.7 ± 741.7) and (5 210.8 ± 1006.8) mg.hL-1, respectively, and t1 / 2 were (1.83 ± 0.29) mg / , (12.9 ± 5.8), (12.2 ± 4.0) and (9.2 ± 2.7) L, respectively. The CL / F were (4.7 ± 1.4) (2.5 ± 0.4), (2.00 ± 0.28) and (2.14 ± 0.24) h respectively, (4.8 ± 1.6) and (4.0 ± 0.7) Lh- Conclusion: The HPLC-MS method can be used to study the pharmacokinetics of mitiglinide in human. Chinese healthy volunteers single dose of oral administration of mitoxantrone plasma concentration - time curve in line with a pharmacokinetic process.