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,5μm),Diamond C18色谱柱(250 mm×4.6mm,5μm),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(Mr)、分子离子峰(m/z)及液相色谱保留时间(tR)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1.60～6.40μg·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。

Structure confirmation,detection and control of impurities for lansoprazole enteric capsules

Objectives: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 de-tection was carried out at wavelength 285 nm.The column oven temperature was maintained at 30 ℃.The relative molecular mass(Mr),mass-to-charge ratio(m/z) and retention time(tR) 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 lanso-prazole enteric capsules.