HPLC检测器联用法测定瑞格列奈二甲双胍片中瑞格列奈的有关物质

第 53 卷第 3 期		Vol. 53 No. 3
2023 年 6 月		Jun 2023

所属栏目：分析与测试

HPLC检测器联用法测定瑞格列奈二甲双胍片中瑞格列奈的有关物质

张琳1，2，3，刘林1，颜红1，邢雪敏1*，刘葵葵1，李欣1 （1. 山东省药学科学院山东省化学药物重点实验室，山东济南 250101；2. 山东福瑞达医药集团有限公司，山东济南 250101；3. 山东省黏膜与皮肤给药技术重点实验室，山东济南 250101）

摘　要：建立二极管阵列及荧光检测器联用的HPLC方法测定瑞格列奈二甲双胍片中瑞格列奈的有关物质。以辛烷基硅烷键合硅胶为填充剂，以磷酸二氢钾缓冲溶液与乙腈为流动相，采用梯度洗脱分离；检测器为二极管阵列与荧光检测器串联，二极管阵列检测器检测波长240 nm，荧光检测器激发波长244 nm、发射波长348 nm；流速1.0 mL/min，进样体积50 μL，柱温40 ℃。两种检测器条件下主峰及各杂质之间分离度均较好；各杂质及瑞格列奈检测限分别为0.012、0.020、0.103、0.088、0.073、0.024 ng/mL，定量限依次为0.053、0.060、0.309、0.264、0.219、0.072 ng/mL；主峰及各杂质在1~50 ng/mL浓度范围内浓度与峰面积线性关系良好；五种杂质的平均回收率为98.3%、94.2%、98.2%、96.5%、103.6%，RSD依次为3.8%、2.6%、4.1%、3.9%、5.6%（n=6）；6份样品中，杂质1平均含量为0.05%，RSD为6.8%，其他已知杂质均未检出，未知杂质未检出；供试品溶液在8 h内稳定性良好。该方法灵敏度高，准确度和重复性均较好，可用于检测瑞格列奈二甲双胍片中瑞格列奈的有关物质。

关键词：瑞格列奈二甲双胍片；瑞格列奈；有关物质；检测器联用法

中图分类号：O657.7　　文献标识码：A　　文章编号：1009-9212（2023）03-0068-05

Determine Repaglinide-related Substances in Repaglinide and Metformin Tablets Using HPLC with Combined Detectors

ZHANG Lin1,2,3, LIU Lin1, YAN Hong1, XING Xue-min1*, LIU Kui-kui1, LI Xin1 (1. Key Laboratory for Chemical Drugs Research of Shandong Province, Shandong Academy of Pharmaceutical Sciences, Ji’nan 250101, China; 2. Shandong Freda Pharmaceutical Group Co., Ltd., Ji’nan 250101, China; 3. Shandong Provincial Key Laboratory of Mucosa and Transdermal Drug Delivery Technology, Ji’nan 250101, China)

Abstract：The related substances of repaglinide in the repaglinide and metformin compound tablets were more accurately determined by HPLC method with diode array and fluorescence detector. Octylsilane-bonded silica gel was used as filler; potassium dihydrogen phosphate buffer solution and acetonitrile were taken as mobile phases, gradient elution was used for separation; the detector was a diode array connected in series with a fluorescence detector, which was used to detect the wavelength 240 nm. Besides, the excitation wavelength of the fluorescence detector is 244 nm; the emission wavelength is 348 nm; the flow rate was 1.0 mL/min；the injection volume was 50 μL; the column temperature was 40 ℃. The repaglinide and other impurities were well separated under the conditions of the two detectors. The limits of detection were 0.012, 0.020, 0.103, 0.088, 0.073, and 0.024 ng/mL, repectively and the limits of quantitation were 0.053, 0.060, 0.309, 0.264, 0.219, and 0.072 ng/mL, respectively. The main peak and each impurity had a good linear relationship between the concentration and the peak area in the concentration range of 1~50 ng/mL.The average recoveries of the 5 impurities were 98.3%, 94.2%, 98.2%, 96.5%, 103.6%. At the same time, the RSD were 3.8%, 2.6%, 4.1%, 3.9%, and 5.6% (n=6). The average content of impurity 1 in six smples was 0.05%, and the RSD was 6.8%. The stability of the test solution was good in the 8 h. This method has high sensitivity, good accuracy and repeatability. Therefore, it can be used to detect the related substances of repaglinide in repaglinide and metformin tablets.

Key words：repaglinide and metformin tablets; repaglinide; related substances; combination detector

作者简介：张琳（1981—），女，山东济南人，高级工程师，硕士，研究方向：药物质量控制（E-mail：25144123@qq.com）。

联系人：邢雪敏，工程师，研究方向：药物质量控制（E-mail：34692577@qq.com）。

收稿日期：2023-03-27