目的: 建立HPLC法测定瑞格列奈片剂中的有关物质,并对5家企业瑞格列奈片的有关物质进行分析。方法: 采用CAPCELL PAK MGⅡC18色谱柱(250 mm×4.6 mm,5 μm),流动相A为磷酸盐缓冲液(0.2%磷酸二氢钾溶液,用磷酸调pH至2.5),流动相B为乙腈,梯度洗脱,流速1 mL·min-1,检测波长240 nm,柱温35 ℃。结果: 瑞格列奈主峰与5个已知杂质峰及其他降解杂质峰分离度良好;瑞格列奈与5个已知杂质分别在各自浓度范围内与峰面积呈良好线性关系(r＞0.999 8,n=6);瑞格列奈和杂质Ⅰ、Ⅱ、Ⅲ、Ⅳ、C定量限分别为0.03、0.02、0.02、0.10、0.05、0.04 μg·mL-1,检测限分别为0.009、0.006、0.006、0.031、0.015、0.012 μg·mL-1;瑞格列奈杂质Ⅰ、Ⅱ、Ⅲ、Ⅳ、C的低、中、高3种浓度的平均回收率分别为100.5%、103.7%、103.5%、104.2%、103.6%。5家企业25批样品的最大单个未知杂质含量为0.03%~0.13%,总杂质含量为0.09%~0.31%。结论: 本法可用于瑞格列奈片有关物质的质量控制。
Objective: To establish an HPLC method for the determination of the related substances of repaglinide tablets, and to analyze the related substances of repaglinide tablets in 5 different companies. Methods: The separation was performed on CAPCELL PAK MGⅡC18(250 mm×4.6 mm,5 μm) with phosphate buffer (0.2% potassium dihydrogen phosphate solution, adjusted to pH 2.5 with dilute phosphoric acid) as mobile phase A, acetonitrile as mobile phase B, and gradient elution flow rate was 1 mL·min-1. The detection wavelength was 240 nm and the column temperature was 35 ℃. Results: The repaglinide and other impurities were well separated. There was a good linear relationship between peak area and the concentration range of repaglinide and 5 known impurities (r＞0.999 8, n=6), respectively. The limits of quantitation were 0.03, 0.02, 0.02, 0.10, 0.05, 0.04 μg·mL-1 for repaglinide, impurity Ⅰ, impurity Ⅱ, impurity Ⅲ, impurity Ⅳ, impurity C, respectively. The limits of detetion were 0.009, 0.006, 0.006, 0.031, 0.015, 0.012 μg·mL-1 for repaglinide, impurity Ⅰ, impurity Ⅱ, impurity Ⅲ, impurity Ⅳ, impurity C, respectively. The average recoveries of impurity Ⅰ, Ⅱ, Ⅲ, Ⅳ and C were 100.5%, 103.7%, 103.5%, 104.2%, 103.6%, respectively. The results of 25 batches of 5 different companies showed that the content of maximum single unknown impurity was 0.03%-0.13%, and the content of total impurities was 0.09%-0.31%. Conclusion: This method can be used for the quality control of related substances of repaglinide tablets.
[1] 徐伟东. 瑞格列奈治疗糖尿病的临床疗效及其安全性[J].临床合理用药杂志, 2018, 11(12):33
XU WD. Clinical efficacy and safety of repaglinide in the treatment of diabetes mellitus[J].J Clin Ration Drug Use, 2018, 11(12):33
[2] 刘蕾. 瑞格列奈片联合二甲双胍治疗妊娠期糖尿病的疗效[J].川北医学院学报, 2019, 34(1):85
LIU L. Therapeutic effect of repaglinide tablets combined with metformin on gestational diabetes mellitus[J].J North Sichuan Med Coll, 2019, 34(1):85
[3] 张悦取, 闫丹彤, 汪娟, 等. HPLC法测定瑞格列奈二甲双胍片中二甲双胍的5种有关物质[J].沈阳药科大学学报, 2018, 35(4):274
ZHANG YQ, YAN DT, WANG J, et al. Determination of five related substances of repaglinide and metformin hydrochloride tablets by HPLC[J].J Shenyang Pharm Univ, 2018, 35(4):274
[4] EP 10.0. Vol Ⅲ[S].2017:3714
[5] BP 2022. Vol Ⅱ[S].2022:806
[6] USP-NF[S/OL]. (2015-05-01) [2022-03-07].https//doi.org/10.31003/USPNF_M73167_01_01
[7] 中华人民共和国药典2020年版. 二部[S].2020:1718
ChP 2020. Vol Ⅱ[S].2020:1718
[8] YBH03892011 国家食品药品监督管理局标准[S].2011
YBH03892011 The State Food and Drug Administration Standard[S].2011
[9] YBH00182013 国家食品药品监督管理局标准[S].2013
YBH00182013 The State Food and Drug Administration Standard[S].2013
[10] YBH00492013 国家食品药品监督管理局标准[S].2013
YBH00492013 The State Food and Drug Administration Standard[S].2013
[11] YBH00372012 国家食品药品监督管理局标准[S].2012
YBH00372012 The State Food and Drug Administration Standard[S].2012
[12] JX20120236 国家食品药品监督管理局进口药品注册标准[S].2012
JX20120236 The State Food and Drug Administration Registration Standards for Imported Drugs[S].2012
[13] 林聪,马红玲,刘丹琦,等. 高效液相色谱法测定瑞格列奈片中的有关物质[J].中南药学, 2013, 11(6):467
LIN C, MA HL, LIU DQ, et al. Determination of the related substances in repaglinide tablets by HPLC[J].Cent South Pharm, 2013, 11(6):467
[14] 马红玲. 瑞格列奈片的处方工艺及质量标准研究[D].长沙:中南大学, 2013
MA HL. Research about Prescription and Quality Standard of Repaglinide Tablets[D].Changsha:Central South University, 2013
[15] 孙浩,蒋素梅,顾萍,等. HPLC法测定瑞格列奈原料药及其片剂中主药和有关物质的含量[J].中国药房, 2007, 18(19):1496
SUN H, JIANG SM, GU P, et al. Determination of repaglinide and the related substances in repaglinide and its tablets by HPLC[J].China Pharm, 2007, 18(19):1496
[16] 李建伟,宋素丽,申爱卓. 加校正因子的主成分自身对照法测定复方片剂中瑞格列奈有关物质[J].药物分析杂志, 2015, 35(8):1488
LI JW, SONG SL, SHEN AZ. Determination of repaglinide related substances in compound tablets with the correction factor and self-contrast method[J].Chin J Pharm Anal, 2015, 35(8):1488
[17] 谢俊霞,白敏,姚冬云, 等. 瑞格列奈片有关物质测定方法的改进[J].科学技术与工程, 2014, 14(7):129
XIE JX, BAI M, YAO DY, et al. Improvement in determination method of relative substances in repaglinide tablets[J].Sci Technol Eng, 2014, 14(7):129
[18] 黄朝辉,蔡丹丹,周征. 不同HPLC检查瑞格列奈片有关物质的对比研究[J].中国现代应用药学, 2016, 33(2):208
HUANG CH, CAI DD, ZHOU Z. Investigation on different HPLC to determine the related substances of repaglinide tablets[J].Chin J Mod Appl Pharm, 2016, 33(2):208
[19] 黄丹,陈冬华,甘加明,等. 国家评价性抽验瑞格列奈片质量分析[J].中国药学杂志, 2021, 56(12):1012
HUANG D, CHEN DH, GAN JM, et al. Quality analysis of repaglinide tablets in national assessment programs[J].Chin Pharm J, 2021, 56(12):1012
[20] 余振喜, 庾莉菊, 黄海伟, 等. 浅谈HPLC法测定有关物质时已知杂质的计算方法[J].中国药品标准, 2010, 11(4):278
YU ZX, YU LJ, HUANG HW, et al. Discussion on the calculation methods of the known impurities in related substances determined by HPLC[J].Drug Stand China, 2010, 11(4):278
