LC-MSMS法测定人血浆中卡络磺钠的浓度01.doc

LC-MS/MS法测定人血浆中卡络磺钠的浓度 赵华，宋敏，杭太俊 (中国药科大学药学院药物分析教研室，南京 210009) 摘要 目的：建立人血浆中卡络磺钠浓度的LC-MS/MS测定法，并用于卡络磺钠的人体药代动力学研究。方法：24名健康志愿者单剂量口服90mg卡络磺钠胶囊，于服药后采血在0. ng?mL-1～ ng?mL-1范围呈现良好线性，方法回收率为.0%～1.0%。内、间精密度RSD分别为%～%和%～。Cmax为(± 8.35) ng?mL-1，Tmax为( ± 0.51) h，t1/2为(± 0.95) h，MRT为( ± 1.09) h，AUC0-8为( ± 25.31) h·ng?mL-1，AUC0-(为( (28.63) h·ng?mL-1，Vz/F为(± 2713.88) L，CL/F为( ± 386.55) L?h-1。结论：健康志愿者单剂量口服90mg卡络磺钠胶囊后，卡络磺钠血浆浓度-时间曲线符合二房室模型。Cmax在9.77 ng?mL-1～ng?mL-1范围，Tmax在0.5 h～by LC-MS/MS ZHAO Hua(, Song Min, HANG Tai-jun (Department of Pharmaceutical Analysis, China Pharmaceutical University, NanJing, 210009，China Abstract Objective: To establish an LC-MS/MS method for the determination of carbazochrome sodium sulfonate in human plasma and study its pharmacokinetics. Methods: A single oral dose of 90 mg carbazochrome sodium sulfonate capsules was given to each of 24 Chinese healthy volunteers. Blood samples were collected before and 0.17，0.33，0.5，0.67，1.0，1.25，1.5，2.0，3.0，4.0, 5.0，6.0, 8.0 h after the administration. The drug plasma concentrations were determined by a validated LC-MS/MS method in APCI positive ion mode. Results: The calibration curve of the LC-MS/MS method was linear in the range of 0.5 ng·mL-1-50 ng·mL-1 with the accuracy from 90% to 105%. The intra-day and inter-day precession (RSD) were 1.18%-1.52% and 5.51%-9.84%, respectively. The main pharmacokinetic parameters of carbazochrome sodium sulfonate after a single oral dose 90mg were as follows, Cmax (20.92± 8.35) ng?mL-1，Tmax (1.16 ± 0.51) h，t1/2 (2.51± 0.95) h，MRT (4.11 ± 1.09) h，AUC0-8 (65.87 ± 25.31) h·ng?mL-1，AUC0-( (75.53 (28.63) h·ng?mL-1，Vz/F (5071.68± 2713.88) L，CL/F (1311.10 ± 386.55) L?h-1. Conclusion: The plasma concentration-time profile of carbazochrome sodium sulfonate fits two compartment models after oral dose of 90 mg capsules. The ranges of Cmax and Tmax were 9.77 ng?mL-1 - 38.88 ng?mL-1 and 0.5h -3h that means there was great individual difference in the absorption and distribution process of carbaz