氟康唑联用咪达唑仑血药浓度测定方法及相互作用  

Determination of Plasma Concentration of Fluconazol and Midazolam Combinations for Children by HPLC Method

作　　者：陆晓彤[1] 刘艳[1] 徐阿晶[1] 舒扬[1] 张春[1] 王芳[1] 林志燕[1] 

机构地区：[1]上海交通大学医学院附属新华医院,上海200092

出　　处：《儿科药学杂志》2012年第11期24-26,共3页Journal of Pediatric Pharmacy

基　　金：上海交通大学医学院科技基金项目;项目编号JYY0904

摘　　要：目的:建立可同时进行氟康唑和咪达唑仑生物样品前处理的方法,应用RP-HPLC法分别测定氟康唑、咪达唑仑、1-羟基咪达唑仑的血药浓度;同时考察氟康唑与咪达唑仑联用对咪达唑仑血药浓度的影响。方法:1 mL血清样品加入内标后以5 mL乙酸乙酯提取,有机相用氮气吹干,以100μL甲醇溶解,分别在不同的色谱条件下以20μL进样测定。结果:氟康唑、咪达唑仑、1-羟基咪达唑仑及内标能够在同一条件下被提取。氟康唑在0.5～20μg/mL范围内线性关系良好(r=0.997 0,n=6),咪达唑仑在0.03～7.29μg/mL范围内线性关系良好(r=0.998 5,n=16),1-羟基咪达唑仑在0.09～7.29μg/mL范围内线性关系良好(r=0.999 3,n=5)。联用氟康唑和咪达唑仑组较单用咪达唑仑组中咪达唑仑血药浓度明显增高。结论:该法灵敏、准确、简单、快速,可用于同时测定氟康唑、咪达唑仑及其代谢产物的血药浓度。联用氟康唑和咪达唑仑与单用咪达唑仑比较,咪达唑仑血药浓度明显增高。Objective：To establish a biological sample pre-treatment method to extract fluconazole and midazolam simultaneously.HPLC methods were separately established to determine fluconazol,midazolam and 1-hydroxymidazolam in serum.Whether the plasma concentration of midazolam affected by fluconzole and midazolam combinations was also investigated in this study.Methods：The blood samples（1 mL） were extracted with ethyl acetate（5 mL）.The organic extract was concentrated to dryness under a mild nitrogen fumes stream.The residue was dissolved in methanol（100 μL）,and 20 μL of it was used for HPLC analyze under different conditions.Results：Fluconazol,midazolam and 1-hydroxymidazolam could be extracted in the same condition.The calibration curves for fluconazol had a good linearity over the range of 0.5～20 μg·mL-1（r=0.9970,n=6）.The calibration curves for midazolam had a good linearity over the range of 0.03～7.29 μg·mL-1（r=0.9985,n=16）.The calibration curves for 1-hydroxymidazolam had a good linearity over the range of 0.09～7.29 μg·mL-1（r=0.9993,n=5）.Compared to the children treated with single in midazolam,the plasma concentration of midazolam in children who were treated with combined fluconazole and midazolam increased significantly.Conclusions：The method is sensitive,accurate,simple,rapid and applicable for clinical plasma drug level monitoring of fluconazol,midazolam and its metabolites.The plasma concentration of midazolam in children who were treated with combined fluconazole and midazolam was higher than that in the children treated only with midazolam.

关 键 词：RP-HPLC法 氟康唑 咪达唑仑 1-羟基咪达唑仑 

分 类 号：R969.3[医药卫生—药理学]