兰索拉唑肠溶胶囊中杂质的结构确证、检查及控制

目的: 建立兰索拉唑肠溶胶囊中杂质的检查方法,进行稳定性考察,确证杂质的结构。 方法: 采用液相色谱进行杂质检查的方法学研究及稳定性考察;采用Supelcosil LC–ABZ色谱柱(250 mm×3.0 mm,5 μm),Diamond C₁₈色谱柱(250 mm×4.6 mm,5 μm),流动相为 1.67 %三乙胺水溶液(用磷酸调pH至 6.2)–乙腈(65∶35),等度洗脱,流速 1.0 mL·min^-1,检测波长 285 nm,柱温 30 ℃。采用液–质联用技术及标准杂质对照法进行杂质的结构确证。通过相对分子质量(M_r)、分子离子峰(m/z)及液相色谱保留时间(t_R)三方面的信息进行杂质的结构确证。 结果: 供试品经强制破坏后各杂质峰与主峰均能达到基线分离。最低检测限 0.05 ng (S/N=3)。不同放置时间主峰峰面积的RSD=0.67 %(n=5);改变流动相pH,主峰峰面积的RSD=0.14 % (n=3);改变柱温,主峰峰面积的RSD=1.4 %(n=3)。杂质E的浓度在 1.60 ~6.40 μg·mL^-1范围内线性良好(r=0.9999)。主峰及各杂质对照峰的峰纯度良好。 结论: 确证了供试品中杂质的结构,建立了杂质检查的方法,此法简便易行,耐用性好,专属性强,灵敏,准确,适用于兰索拉唑肠溶胶囊剂中杂质的确证、检查及控制。

Objective: To establish an HPLC method of the detection and control of impurities in lansoprazole enteric capsules;To perform stability studies on lansoprazole enteric capsules and structure confirmation of impurities. Methods: Supelcosil LC-ABZ (250 mm×3.0 mm,5 μm) and Diamond C₁₈ chromatographic column (250 mm×4.6 mm,5 μm) were adopted;The mobile phase consisted of a mixture of 1.67 % triethylamine aqueous solution (adjusted to pH 6.2 using phosphoric acid)–acetonitrile(65∶35) with a flow rate of 1.0 mL·min^-1,the UV detection was carried out at wavelength 285 nm.The column oven temperature was maintained at 30 ℃.The relative molecular mass(M_r),mass-to-charge ratio(m/z) and retention time(t_R) were applied to confirm the structure of impurities in lansoprazole enteric capsules by comparison with impurity reference substances. Results: The lowest detection limit of the method was 0.05 ng (S/N=3),The calibration curve of impurity E was linear in the range of 1.60-6.40 μg·mL^-1(r=0.9999). Conclusions: An isocratic stability-indicating RP-HPLC method has been developed and validated of the detection and control of impurities in lansoprazole enteric capsules;Stability studies on lansoprazole enteric capsules were performed,and the structures of impurities have confirmed.This method is selective,specific,good durable.It is suitable for structure confirmation,detection and control of impurities in lansoprazole enteric capsules.