摘要
目的建立液相色谱-串联质谱(LC-MS/MS)电喷雾检测法快速测定血浆中头孢哌酮浓度的方法,并研究其在健康人体内的药动学。方法采用LC-MS/MS法测定健康志愿者静脉滴注后不同时间血浆中头孢哌酮的浓度。以克仑特罗为内标,采用Agilent Zorbax SB C18(100 mm×3.0 mm,3.5μm)进行分离,通过串联质谱仪,以选择反应监测方式进行测定。用于定量分析的离子对分别为m/z 668→526(头孢哌酮)和m/z 277→203(克仑特罗)。结果头孢哌酮血药浓度在0.507~202.80 mg·L-1范围内线性关系良好(r2=0.999 7),最低定量限为0.507 mg·L-1,相对回收率均大于90%,日内和日间RSD均小于10%。单剂量静脉滴注头孢哌酮1.5 g,t1/2为(1.77±s 0.28)h,MRT为(2.34±0.12)h,AUC0~10为(300±56)mg·h·L-1。结论本方法快速、简便、准确、灵敏,适用于头孢哌酮的人体药动学研究。
AIM To establish an LC-MS/ MS electrospray ionization method for swift determination of plasma cefoperazone concentration and to study the correlative pharmacokinetics in healthy volunteers.METHODS The concentrations of cefoperazone in the plasma of healthy volunteers after different time points of intravenous drip were determined by LC-MS / MS.Taking clenbuterol as internal standard,the plasma was separated with Agilent Zorbax SB C18 column(100 mm × 3.0 mm,3.5 μm).A tandem mass spectrometer equipped with ESI was used as detector and operated in the positive ion mode.Selected reaction monitoring (SRM) using the precursor product ion combinations of m / z 668 →526 and m / z 277 →203 was taken quantitative analysis of cefoperazone and the internal standard respectively.RESULTS The established method was able to determine cefoperazone in human plasma and to select the range of 0.507-202.80 mg·L-1 as the best linear correlation with the lowest limit at 0.507 mg·L-1(r2 = 0.999 7).Relative recovery rate ranged from 93.02% to 103.89% with average rate great than 90%.Within-day RSD and between-day RSD were less than 10%.After intravenous drip of single 1.5 g dose,the values of t1/ 2,MRI and AUC0-10 were(1.77 ± s 0.28) h,(2.34 ± 0.12) h,and(300 ± 56) mg·h·L-1,respectively.CONCLUSION LC-MS/MS method for determination of plasma cefoperazone and study of the pharmacokinetics is quick,simple,accurate and sensitive.
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2010年第5期345-349,共5页
Chinese Journal of New Drugs and Clinical Remedies
关键词
头孢哌酮
色谱法
高压液相
光谱法
质量
电喷雾电离
药动学
cefoperazone
chromatography
high pressure liquid
spectrometry
mass
electrospray ionization
pharmacokinetics