LC-MS/MS法测定人血浆中的替加色罗及其药动学

Determination of tegaserod in human plasma by LC-MS/MS and study on its pharmacokinetics

目的建立人血浆中替加色罗LC-MS/MS测定法,进行人体药动学研究。方法测定24名健康受试者口服受试制剂(单剂量、多剂量)后血浆中替加色罗浓度。结果单剂量口服替加色罗(4、6、12mg)后药动学参数:t(1/2)β为(2.92±0.89)、(3.81±0.84)、(3.3±0.47)h;t_(max)为(1.06±0.28)、(1.00±0.26)、(1.00±0.18)h;ρ_(max)为(1.23±0.47)、(2.34±0.60)、(4.24±1.71)μg·L^(-1);AUC_(0→12)为(3.04±0.91)、(5.21±1.13)、(9.29±3.37)μg·h·L^(-1);MRT为(3.57±0.81)、(3.91±0.65)、(3.34±0.48)h;替加色罗多剂量(6mg,bid)药动学参数t_(max)为(0.96±0.10)h,ρss_(max)为(2.60±0.53)μg·L^(-1),pss_(min)为(0.07±0.01)μg·L^(-1),ρ_(av)为(0.51±0.11)μg·L^(-1),AUC_(0→12)为(6.13±1.3)μg·h·L^(-1)。结论本方法结果准确、灵敏,替加色罗在大部分人体内的过程符合二室开放模型,其主要药动学参数与国内外文献相近。

AIM To study the pharmacokinetics of tegaserod in human plasma by LC-MS/MS.METHODS Twenty-four healthy volunteers received tegaserod tablets （single doses,multidose）,drug concentrations in plasma were determined.RESULTS Pharmacokinetic parameters of tegaserod after single oral doses （4,6,12 mg）were as follows： t（1/2）β（2.92±0.89）,（3.81 ±0.84）and （3.3±0.47）h;tmax（1.06±0.28）,（1.00±0.26）and （1.00±0.18）h;ρmax（1.23±0.47）,（2.34 ± 0.60）and （4.24 ± 1.71）μg·L^-1AUC0→12（3.04 ± 0.91）,（5.21±1.13）and （9.29 ± 3.37）μg·h·L^-1MRT （3.57 ± 0.81）,（3.91 ± 0.65）and （3.34±0.48）h,the essential pharmacokinetic parameters after oral multidose （6 mg,bid）were as follows：tmax（0.96±0.10）h,ρssmax（2.60±0.53）μg·L^-1ρssmin, （0.07 ±0.01）μg·L^-1ρav（0.51 ±0.11）μg·L^-1AUC0→12（6.13±1.3）μg·h·L^-1CONCLUSION The method is accurate,sensitive.A two-compartment open pharmacokinetic model is adapted to tegaserod plasma concentration-time data analysis.The main phannacokinetic parameters are similar to those reported domestically and abroad.