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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 method for the simultaneous preconditioning of fluconazole and midazolam, and to determine the plasma concentration of fluconazole, midazolam and 1-hydroxy midazolam by RP-HPLC simultaneously. To investigate the effects of fluconazole and midazolam on plasma concentrations of midazolam. Methods: 1 mL of serum sample was added with 5 mL of ethyl acetate after extraction of the internal standard. The organic phase was blown dry with nitrogen and dissolved in 100 μL of methanol. The concentration of 20 μL was determined under different chromatographic conditions. Results: Fluconazole, midazolam, 1-hydroxy midazolam and internal standard can be extracted under the same conditions. Fluconazole had a good linearity (r = 0.997 0, n = 6) in the range of 0.5-20 μg / mL and a good linear relationship of midazolam in the range of 0.03-7.29 μg / mL (r = 0.998 5, n = 16 ), 1-hydroxy midazolam in the range of 0.09 ~ 7.29μg / mL good linear relationship (r = 0.999 3, n = 5). Midazolam plasma concentrations of fluconazole and midazolam group were significantly higher than those of midazolam alone group. Conclusion: The method is sensitive, accurate, simple and rapid and can be used for the simultaneous determination of plasma concentrations of fluconazole, midazolam and its metabolites. Compared with single midazolam, fluconazole and midazolam combined, midazolam plasma concentration was significantly higher.