高效液相色谱法测定犬血浆中雷诺嗪的含量及相对生物利用度

Determination of ranolazine in Beagle dog plasma by HPLC-UV method

目的建立测定Beagle犬血浆中雷诺嗪浓度的高效液相色谱-紫外检测方法。方法血浆样品中加入内标苯海拉明,经氢氧化钠溶液碱化后用乙醚提取。色谱柱为Diamonsil C_(18)(250mm×4.6mm,5μm),流动相为甲醇-含醋酸胺50mmol·L^(-1)水溶液(58:42,V/V),柱温为50℃,流速为1.0 mL·min^(-1),测定波长为270nm。采用BAPP2.0程序计算雷诺嗪普通片和缓释片的药动学参数。结果雷诺嗪在0.04～2.56mg·L^(-1)范围内线性关系良好,定量下限为0.04mg·L^(-1),提取回收率为92%～97%,批内、批间RSD均小于10%。雷诺嗪缓释片的相对生物利用度为(102±14)%。结论本方法操作简便、准确、重现性好,符合生物样品的分析要求,可以用于雷诺嗪的生物利用度研究。

AIM To establish a HPLC-UV method for the determination of ranolazine in Beagle dog plasma. METHODS Diphenhydramine was selected as internal standard （IS）. After addition of IS, plasma samples were alkalized by sodium hydroxide and finally were extracted by ether. The chromatographic separation was performed on Diamonsil C18 （250mm×4.6mm,5μm） column with a mobile phase of methanol-50 mmoL·L^-1 ammonium acetate （58 ： 42, V/V） at a flow rate of 1.0 mL·min^-1. The column temperature was 50 ℃ and the detection wavelength was 270 nm. The pharmacokinetics parameters and the bioeguivalemce of ranolazine tablets and sustained release tablets by the BAPP 2.0 program. RESULTS The concentration ranges of calibration curves for ranolazine （0.04 - 2.56 mg· L^-1） showed good linear correlation. The limit of quantitation was 0.04 mg·L^-1. The extraction recovery was 92% - 97%. Within-day RSD and between-day RSD were less than 10%. The bioeguivaleuce of ranolazine sustained release tablets was （102 ± 14） %. CONCLUSION This method is simple, accurate and reproducible, and is suitable for bioavailability studies.