反相高效液相色谱法同时测定伊马替尼及伏立康唑血药浓度

目的:建立同时测定人血浆中伊马替尼及伏立康唑浓度的高效液相色谱法。方法:血桨样品经乙酸乙酯-正己烷(75∶25)萃取,选择卡马西平为内标,氮吹浓缩、复溶后采用HPLC分析。ZORBAX SB-C18柱反相柱(250 mm×4.6 mm,5μm)为色谱柱,流动相为甲醇-乙腈-醋酸铵缓冲液(25 mmol·L^-1 CH_3COONH_4,CH_3COOH调pH值至4.5)=20∶32∶48(V/V/V),检测波长264 nm,流速为1 mL·min^-1,柱温35℃,进样量为20μL。结果:伊马替尼、伏立康唑血药浓度线性范围分别为0.10~5.00μg·mL^-1和0.10~6.00μg·mL^-1,两者的线性均良好(r分别为0.998和0.999),最低定量下限均为0.10μg·mL^-1。伊马替尼和伏立康唑低、中、高质量浓度的提取回收率分别为69.21%,71.23%,73.53%和76.23%,78.12%,79.34%,二者批内RSD均小于15%。结论:该方法简便、快速、灵敏度高可满足同时检测伊马替尼和伏立康唑的临床血药浓度监测及药动学研究。

Simultaneous detection of concentrations of imatinib and voriconazole in human serum by RP-HPLC

OBJECTIVE To establish a method for determining the concentrations of imatinib and voriconazole in plasma by HPLC. METHODS Blood samples were pretreated by using ethyl acetate-n-hexane (75:25) with carbamazepine as the internal standard, then concentrated by nitrogen and detected by HPLC after dissolution. Analytical column was ZORBAX SB-C₁₈ (250 mm×4.6 mm, 5 mm), mobile phase was methanol-acetonitrile-ammonium acetate buffer (0.025 mol·L^-1 CH₃COONH₄, pH value was adjusted to about 4.5 by CH₃COOH)=20:32:48(V/V/V) at a flow rate of 1.0 mL·min^-1. Detection wavelength was set at 264 nm and temperature was kept at 35℃, and the injection volume was 20 μL. RESULTS The calibration graphs were linear in range of 0.10-5.00 μg·mL^-1 for imatinib and 0.10-6.00 μg·mL^-1 for voriconazole (R=0.998 and 0.999, respectively). Limits of quantification were 0.1 μg·mL^-1 both for imatinib and voriconazole. Extraction recoveries of low, medium and high concentrations were 69.21%, 71.23%, 73.53% for imatinib and 76.23%, 78.12%, 79.34% for voriconazole, respectively. Intra-and inter-day RSD values were less than 15%. CONCLUSION The method is simple, quick and sensitive for drug monitoring and pharmacokinetics study on imatinib and voriconzole.