Paliwal J K, Gupta R C, Grover P K
Pharmacokinetics and Metabolism Division, Central Drug Research Institute, Lucknow, India.
J Chromatogr. 1993 Jun 23;616(1):155-60. doi: 10.1016/0378-4347(93)80483-k.
Compound 80/53 (I) is a new substance being developed as an antimalarial agent. It is unstable in acidic conditions where it is converted into primaquine. A high-performance liquid chromatographic assay for simultaneous determination in serum of I and primaquine has been developed. Conditions were optimized to minimize the conversion of I into primaquine. The method includes extraction of the unchanged compound and primaquine from serum samples with hexane-2-propanol (pH > 8). Separation was accomplished by reversed-phase chromatography on a C18 column with acetonitrile-tetrahydrofuran-phosphate buffer. The recoveries of I and primaquine were always greater than 70%. No interference was observed in extracts obtained from drug-free serum. The detector response was linear with concentrations of I and the metabolite in the ranges 25-400 and 10-180 ng/ml, respectively, and the within-day precision (coefficient of variation) remained less than 13.7% for I and 12.5% for primaquine. The method is suitable for the determination of concentration-time profiles of I and primaquine in human serum.
化合物80/53（I）是一种正在开发的新型抗疟药。它在酸性条件下不稳定，会转化为伯氨喹。已开发出一种高效液相色谱法，用于同时测定血清中的I和伯氨喹。对条件进行了优化，以尽量减少I向伯氨喹的转化。该方法包括用己烷 - 2 - 丙醇（pH > 8）从血清样品中提取未变化的化合物和伯氨喹。通过在C18柱上进行反相色谱分离，流动相为乙腈 - 四氢呋喃 - 磷酸盐缓冲液。I和伯氨喹的回收率始终大于70%。在从不含药物的血清中获得的提取物中未观察到干扰。检测器响应与I及其代谢物浓度分别在25 - 400 ng/ml和10 - 180 ng/ml范围内呈线性关系，I的日内精密度（变异系数）保持在13.7%以下，伯氨喹为12.5%。该方法适用于测定人血清中I和伯氨喹的浓度 - 时间曲线。
