目的: 建立HPLC法测定格列美脲原料药中间体的有关物质。方法: 采用五氟苯基键合硅胶(150 mm×4.6 mm,2.7 μm)色谱柱,以磷酸二氢铵缓冲溶液-乙腈为流动相,等度洗脱,流速0.5 mL· min-1,柱温25 ℃,检测波长225 nm。结果: 格列美脲中间体与4个已知杂质A~D色谱峰均能良好分离,并分别在0.008~6.024 μg·mL-1(r=0.999 9)、0.005~6.013 μg·mL-1(r=0.999 6)、0.011~5.987 μg·mL-1(r=0.999 8)、0.012~6.045 μg·mL-1(r=0.999 8)、0.029~5.989 μg·mL-1(r=0.999 6)范围内线性关系良好(n=6)。格列美脲中间体、杂质A、杂质B、杂质C、杂质D的定量限分别为8.3、5.0、10.6、11.9、29.4 ng·mL-1;杂质A~D平均回收率(n=9)分别为107.0%、100.0%、98.0%、101.6%。6批格列美脲中间体样品测定结果显示,已知杂质及其他最大单个杂质含量均小于0.50%,杂质总量小于1.0%。结论: 经方法学验证,本方法灵敏、快速,专属性强,准确度高,可用于格列美脲原料药中间体有关物质的测定。
Objective: To establish an HPLC method for the determination of the related substances in glimepiride intermediate. Methods: The determination was performed on a pentafluorophenyl column(150 mm×4.6 mm,2.7 μm). The mobile phase consisted of ammonium dihydrogen phosphate buffer solution and acetonitrilewith isocratic elution.The flow rate was 0.5 mL·min-1, and the column temperature was 25 ℃, the detection wavelengthwas set at 225 nm. Results: The resolutions between the peaks of glimepiride intermediate and four knownimpurities(including impurities A-D)were good. The calibration curves of glimepiride intermediate and the known impurities were linear in the ranges of 0.008-6.024 μg·mL-1(r=0.999 9)、 0.005-6.013 μg·mL-1(r=0.999 6), 0.011-5.987 μg·mL-1(r=0.999 8), 0.012-6.045 μg·mL-1(r=0.999 8)、 0.029-5.989 μg·mL-1(r=0.999 6). The limits of quantitation were 8.3, 5.0, 10.6, 11.9, 29.4 ng·mL-1. The recoveries (n=9) were 103.2%,100.0%, 98.6%, 99.9% for the impurities A-D, respectively. The determination results of the sixbatches of glimepiride intermediate samples showed that the known impurities were less than 0.10%, the maximum single unknown impurity was less than 0.10%,and the total impurity was less than 0.15%. Conclusion: The method is proved to be simple, rapid and accurate, and can be used for the determination of relatedsubstances in Glimepiride intermediate.
[1] 黄泽凯. 格列美脲联合二甲双胍对老年2型糖尿病血糖控制的影响[J].黑龙江医药, 2021, 34(2):372
HUANG ZK. Effect of glimepiride combined with metformin on blood glucose control in elderly patients with type 2 diabetes mellitus [J].Heilongjiang Med, 2021, 34(2):372
[2] 江苏万邦生化医药股份有限公司.格列美脲原料的制备方法:中国,200810207449.X [P].2009-07-22
Jiangsu wanbang biochemical medicine Co., Ltd. Preparation Method of Glimepiride Raw Material:China, 200810207449.X[P].2009-07-22
[3] 沧州那瑞化学科技有限公司.格列美脲原料药的制备方法:中国,200910070764.7 [P].2010-03-17
Cangzhounarui Chemistry Technology Co., Ltd. Preparation Method of Glimepiride Bulk Drug:China, 200910070764.7 [P]. 2010-03-17
[4] 重庆康刻尔制药股份有限公司.一种格列美脲原料药的精制方法:中国,202010791655.0[P].2020-12-04
Chongqing Kangkeer Pharmacy co., ltd. Refining Method of Glimepiride Bulk Drug:China, 202010791655.0 [P].2020-12-04
[5] 北京悦康科创医药科技股份有限公司.一种格列美脲中间体及其异构体的分离方法和合成方法:中国,201910860635.1[P].2019-11-29
Beijing Yuekangke Chuang Medicine Technology Co., Ltd. Separation Method and Synthesis Method of Glimepiride Intermediate and Isomer There of:China, 201910860635.1 [P].2019-11-29
[6] 杨文智,李霞霞,王树根,等. 格列美脲水凝胶剂体内外透皮释放的评价[J].河北大学学报(自然科学版),2015,35(6):599
YANG WZ, LI XX, WANG SG, et al. Evaluation of transdermal release of glimepiride hydrogel in vitro and in vivo[J].J HebeiUniv (Nat Sci Edit), 2015, 35(6):599
[7] 扬子江药业集团江苏海慈生物药业有限公司.格列美脲关键中间体的合成方法:中国,201710719291.3 [P].2017-11-24
Yangzijiang Pharmaceutical Group Jiangsu Haici Biology Drug Co., Ltd. Synthesis method of key intermediate of glimepiride:China,201710719291.3 [P].2017-11-24
[8] GURJAR MK, JOSHI RA, CHAUDHURI SR, et al. Total synthesis of cis and trans-hydroxyglimepiride:active metabolite of glimepiride[J].Chem Inf, 2003, 34(26):4853
[9] 沧州那瑞化学科技有限公司.格列美脲关键中间体的合成方法:中国,200910075764.6 [P].2011-02-23
Cangzhou Narui Chemistry Technology Co., Ltd. Synthesis Method of Key Intermediate of Glimepiride:China,200910075764.6[P].2011-02-23
[10] 山东新华制药股份有限公司.格列美脲中间体磺酰胺类似物1和磺酰胺类似物2的制备方法:中国,201910307697.X [P].2019-06-11
Shandong Xinhua Pharmaceutical Co., Ltd. Preparation Method of Glimepiride Intermediates Sulfonamide Analog 1 and Sulfonamide Analog 2:China, 201910307697.X[P].2019-06-11
[11] 中华人民共和国药典2020 年版.四部[S].2020:374
ChP2020.Vol Ⅳ[S].2020:374
[12] ICH. Q2(R1)Validation of Analytical Procedures:Text andMethodology[S].2005
[13] ICH. Q3A(R2) Harmonized Tripartite Guideline:Impurities in New DrugSubstances[S].2006
[14] 牛冲,刘明洁,凌霄,等. HPLC测定格列美脲有关物质的改进[J].中国现代应用药学,2013,30(5):522
NIU C, LIU MJ, LING X, et al. Improvement of HPLC determination of related substances in glimepiride[J].Chin J Mod Appl Pharm, 2013, 30(5):522
[15] 黄瑛,易秋艳,杨蕾,等.格列美脲胶囊有关物质检查方法的研究[J].药物分析杂志,2003,23(5):351
HUANG Y,YI QY,YANG L, et al. Study on the method for examination of related substances in glimepiride capsules[J].Chin J Pharm Anal, 2003, 23(5):351
[16] 魏君,王维贤,高立军,等.格列美脲原料药中有关物质及降解产物的研究[J].药物分析杂志,2003,23(3):207
WEI J, WANG WX, GAO LJ, et al. Study on related substances and degradation products in glimepiride bulk drug[J].Chin J Pharm Anal, 2003, 23(3):207
