论文部分内容阅读
目的建立同时测定大鼠血浆中曲马多、O-去甲基曲马多、N-去甲基曲马多、N,O-二去甲基曲马多和异丙嗪的UPLC-MS方法,并将其应用于复方盐酸曲马多和盐酸异丙嗪注射液在大鼠体内的药动学研究。方法采用沉淀蛋白法进行样品预处理,色谱柱为Acquity UPLC BEH C18(50 mm×2.1 mm,1.7μm)柱,流动相采用乙腈-5 mmol·L~(-1)醋酸铵(含体积分数0.02%甲酸溶液)梯度洗脱,以正离子选择离子监测模式进行检测。结果血浆中曲马多、O-去甲基曲马多、N-去甲基曲马多、N,O-二去甲基曲马多和异丙嗪分别在质量浓度为1.84~368.0μg·L~(-1)、0.21~42.00μg·L~(-1)、0.49~98.00μg·L~(-1)、0.48~96.00μg·L~(-1)和1.90~380.0μg·L~(-1)内线性关系良好,日内和日间精密度RSD均不超过10.8%,提取回收率为93.2%~109.5%,基质效应为93.3%~104.6%,5个分析物的血浆样品在所考察的储存条件下均可保持稳定。结论该方法适用于复方盐酸曲马多和盐酸异丙嗪注射液在大鼠体内的药动学研究。与单独给药后的药动学行为进行比较,复方同时给药后,曲马多及其3个代谢物的ρmax和AUC均增加,特别是在雌性大鼠体内;而复方给药后,曲马多对异丙嗪的药动学行为无明显影响。
OBJECTIVE To establish a UPLC-MS method for the simultaneous determination of tramadol, O-desmethyltramadol, N-desmethyltramadol, N, O-didemethyl tramadol and promethazine in rat plasma , And its application in the pharmacokinetics of compound tramadol hydrochloride and promethazine hydrochloride injection in rats. Methods Precipitation protein was used for sample pretreatment. The column was Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 μm). The mobile phase was acetonitrile-5 mmol·L -1 ammonium acetate (volume fraction 0.02 % Formic acid solution) gradient elution, positive ion selective ion monitoring mode detection. Results The levels of tramadol, O-desmethyltramadol, N-desmethyltramadol, N, O-demethyltramadol and promethazine in the plasma were respectively measured at the mass concentration of 1.84-368.0 μg · L -1, 0.21-42.00 μg · L -1, 0.49-98.00 μg · L -1, 0.48-96.00 μg · L -1 and 1.90-380.0 μg · L -1, respectively. (-1). The RSD of intra-day and inter-day precision was no more than 10.8%. The extraction recovery was 93.2% -109.5% and the matrix effect was 93.3% -104.6%. The plasma concentrations of five analytes were Investigate the storage conditions can be stable. Conclusion This method is suitable for the study of pharmacokinetics of compound tramadol hydrochloride and promethazine hydrochloride injection in rats. Compared with the pharmacokinetic behavior after single administration, the mean ρmax and AUC of tramadol and its three metabolites increased after the simultaneous administration of compound, especially in female rats. After compound administration, Maduo on promethazine pharmacokinetics had no significant effect.