LC-ESI/MS法测定血浆中头孢他美浓度及头孢他美酯分散片相对生物利用度的研究

Determination of cefetamet in human plasma by LC-ESI/MS and study on the relative bioavailability of cefetamet pivoxil dispersible tablets

目的:建立快速、简捷、灵敏的LC-ESI/MS法测定人血浆中头孢他美的浓度,并用于头孢他美酯分散片的药代动力学与生物等效性的研究。方法:血浆样品经沉淀处理后以乙腈-0.4%甲酸水溶液(65∶35)为流动相,采用ESI源以SIM方式对血浆样品中头孢他美进行定量分析。结果:研究结果表明,头孢他美血浆浓度测定方法的线性范围为0.05～8μg·mL-1,日内、日间精密度(RSD)均小于12.33%,方法回收率(RE)为-3.40%～12.26%,提取回收率大于80%。供试制剂与参比制剂的药代参数分别为:T1/2(2.52±0.54)h和(2.35±0.62)h,Tmax(2.35±0.65)h和(2.33±0.77)h,Cmax(3.33±1.99)mg·L-1和(3.15±1.00)mg·L-1,AUC0-t(17.04±4.75)mg·h·L-1和(16.45±4.61)mg·h·L-1,AUC0-∞(17.61±4.82)mg·h·L-1和(16.95±4.72)mg·h·L-1。生物利用度为(104.30±11.50)%。结论:本法满足生物样本的分析要求,可用于头孢他美酯分散片的生物等效性与药代动力学研究。

Objective：To establish a rapid and sensitive liquid chromatography -electrospray ionization -mass spectrometry （ LC - ESI/MS） method for quantification of cefetamet in human plasma which could be applied for the bioequivalence and pharmaeokineties study of eefetamet pivoxil dispersible tablets. Methods： After protein precipita- tion, the analysis was performed in selected ion monitoring（ SIM ）mode with a positive eleetrospray ionization （ESI） interface with a mobile phase consisting of aeetonitrile and 0.4% formic acid water solution （65：35 ）. Results：The linear concentration range of the calibration curve was 0.05 - 8 μg . mL- 1 for cefetamet, inter - and intra - preci- sions（RSDs） were both less than 12.33%, accuracy（RE） was within- 3.40% -12.26% and absolute recovery was more than 80%. The pharmacokinetlc parameters of the trial preparation or the reference preparation were T1/2 （2.52 ±0.54）h and（2.35 ±0.62）h,T_max（2,35 ±0.65）h and（2.33 ±0.77）h,C_max（3.33 ± 1.99 ）mg . L-1and （3.15±1.00）mg . L-1,AUC0-t（17.04±.4.75）mg . h .L-1 and（16.45 ±4.61）mg . h . L-1,AUC0- ∞（ 17.61 ±4.82 ）mg . h . L-1 and （ 16, 95 ± 4.72） mg. h .L-1. The relative bioavailability was （ 104.30 ± 11.50） %. Conclusion： The method is suitable for pharmaeokinetic and bioequivalenee study of cefetamet pivoxil dispersible.