LC-MS/MS法测定鲁比前列酮软胶囊的溶出度

目的: 建立LC-MS/MS法测定鲁比前列酮软胶囊的溶出度。方法: 以15-羟基十五酸为内标物,以乙醚进行液-液萃取。采用Waters XTerra MS C₁₈(100 mm×2.1 mm,5 μm),以5 mmol·L^-1乙酸铵(含0.02%乙酸)为流动相A相,以甲醇-乙腈(65:35,含0.02%乙酸)为流动相B,进行梯度洗脱;采用电喷雾离子源(ESI)、负离子模式检测,多反应监测(NMR)方式定量分析。结果: 鲁比前列酮在10~200 ng·mL^-1范围内线性良好(r=0.999 8);最低检测限为3 ng·mL^-1;平均回收率(n=9) 为100.1%,RSD为1.7%;日内与日间的精密度RSD均小于10%。3批自制胶囊与市售胶囊溶出曲线的拟合度f分别为73.81、59.12和80.17。结论: 自制胶囊溶出行为与市售胶囊一致。本法经方法学验证,可用于测定鲁比前列酮软胶囊的溶出度。

Objective: To establish an LC-MS/MS method for the quantitative determination of dissolution of lubiprostone capsules. Methods: 15-hydroxypentadecanoic acid was adopted as internal standard and ether was used as the liquid-liquid extraction solvent.A Waters XTerra MS C₁₈ was applied with the mobile phase of 5 mmol·L^-1 ammonium acetate(containing 0.02% acetic acid) to A phase and methanol-acetonitrile(65:35) containing 0.02% acetic acid to B phase by gradient elution.Eectrospray ionization (ESI) source was employed and the analytes were detected by multiple reaction monitoring (NMR) scanning under the negative ionization mode. Results: The calibration curve of lubiprostone was linear in the range of 10-200 ng·mL^-1(r=0.999 8);the lowest detection limit was 3 ng·mL^-1;the average recovery(n=9) was 100.1% with RSD of 1.7%;RSDs of intra-day and inter-day precision were less than 10%,respectively.The dissolution of goodness of fit of 3 batches of homemade and commercially available capsules were 73.81,59.12 and 80.17,respectively. Conclusion: The dissolution behavior of homemade capsules is consistent with commercial capsules.The established method is accurate,sensitive,reproducible and precision,which can be applied to the dissolution determination of lubiprostone capsules.