HPLC/MS测定环孢素A单用及联用氟康唑的血药浓度  

Determination of the blood concentration of cyclosporine A alone and in combination with fluconazole by HPLC/MS

作　　者：易林高[1] 吴明钗[1] 黄鹏[1] 陈晓孩[1] 陆日鸣 

机构地区：[1]瑞安市人民医院药学部,浙江温州325200 [2]温州医科大学仁济学院,浙江温州325035

出　　处：《中国药物应用与监测》2016年第4期211-213,共3页Chinese Journal of Drug Application and Monitoring

基　　金：浙江省药学会医院药学专项科研资助项目(2013ZYY14)

摘　　要：目的:建立质谱法测定环孢素A(CsA)的血药浓度,并用其测定CsA单/联用氟康唑的血药浓度。方法:采用液质联用法测定单/联用氟康唑时CsA的血药浓度,色谱柱:Agilent Zorbax SB-C_(18)柱,柱温50℃,流动相为乙腈-0.1%甲酸,流速0.5 m L·min^(-1);质谱条件:ESI(电喷雾离子源),正离子检测,雾化气压力设为20 psi。结果:CsA在100~20 000 ng·m L^(-1)内线性关系良好(r=0.999 6),日内、日间RSD均低于5%,平均萃取回收率为90%;联合使用氟康唑的CsA比单独使用CsA在第5天血药谷浓度平均高178.0%,峰浓度平均高161.3%。结论:本方法简便、专属、准确、灵敏度高,可用于CsA血药浓度测定及药动学的研究;正在联合使用CsA和氟康唑的患者,氟康唑会明显增高CsA的血药浓度,应减少CsA的用量,并密切监测CsA的血药浓度。Objective： To establish a mass spectrometry method for determination of blood concentration of cyclosporine A（CsA）, and determine the blood concentration of cyclosporine A alone and in combination with fluconazole. Methods： The blood concentration of cyclosporine A in rats was detected and compared when cyclosporine alone and combined with fluconazole by using liquid chromatography-mass spectrometry. Chromatographic column Agilent Zorbax SB-C18 was used. Column temperature was 50 ℃. Mobile phase was acetonitrile-0.1% formic acid. Flow rate was 0.5 m L·min^-1. Mass spectrometry condition was as follows： ESI（electrospray ion source） was used, positive ion detection was used, atomizing gas pressure was set to 20 psi. Results： The linear relationship of CsA was good in the range of 100 – 20 000 ng·m L^-1（r = 0.999 6）. Intra-day RSD and inter-day RSD were less than 5%. The average extraction recovery was 90%. The average blood trough concentration of CsA when CsA combined with fluconazole was higher（by 178.0%） than just cyclosporine alone in five days, and the peak concentration in combined utilization was higher（by 161.3%） than that of alone use. Conclusion： The method is simple, specific, accurate and high sensitivity, which can also be used for the determination of CsA blood concentration and pharmacokinetics study. Patients who are using Cs A and fluconazole will obviously have high blood concentrations of CsA, should reduce the dosage of CsA, and monitor the blood concentration.

关 键 词：环孢素A 氟康唑 含量测定 血药浓度 

分 类 号：R969[医药卫生—药理学]