HPLC法测定维格列汀原料药中的有关物质

目的：建立维格列汀原料药有关物质的HPLC 测定方法。方法：采用Agilent Eclipse Plus C18 色谱柱（4.6 mm×250 mm，5 μm）对降解杂质和工艺杂质进行定量分析，以10 mmol·L^-1 辛烷磺酸钠（加入0.1%磷酸调pH 至2.1）- 乙腈为流动相，梯度洗脱，流速1.0 mL·min^-1，检测波长为210 nm。结果：主峰与各杂质峰间能达到基线分离，维格列汀质量浓度在1.521 0~20.280 μg·mL^-1 范围内与峰面积呈良好的线性关系（r=0.999 8），最低检测限为0.5 μg·mL^-1；3 批样品有关物质测定结果显示，已知杂质含量均低于0.1%。结论：方法学验证结果表明，本法可作为维格列汀质量控制的方法。

Objective:To establish an HPLC method for determination of the related substances in vildagliptin. Methods:The test for degradation and process impurities was based on an Agilent Eclipse Plus C18(4.6 mm×250 mm, 5 μm)column;the mobile phase consisted of 10 mmol·L^-1 sodium octanesulfonate solution(adjusted to pH 2.1 with 0. 1% phosphoric acid)-acetonitrile with gradient elution at the flow rate of 1.0 mL·min^-1;the detection wavelength was 210 nm.Results:Chief peak and every impurity peak were separated well.A good linearity was observed over the range of 1.521 0-20.280 μg·mL^-1(r=0.999 8),the LOD was 0.5 μg·mL^-1;The determination results of the three batch of samples showed that the impurity were less than 0.1%.Conclusion:Methodology validation results proved that the established determination method can be used for quality control of vildagliptin.

[1] ISHII M, SHIBATA R, KONDO K, et al.Vildagliptin stimulates endothelial cell network formation and ischemia-induced revascularization via an endothelial nitric-oxide synthase-dependent mechanism[J].J Biol Chem, 2014, 289(39):27235
[2] JX20100243 State Food and Drug Administration Registration of Imported Drug(国家食品药品监督管理局进口药品注册标准)[S].2010
[3] 刘甦苏, 吴曦, 周舒雅, 等.3 种小鼠品系的四氧嘧啶糖尿病模型建立及初步评价[J].药物分析杂志, 2015, 35(11):1958 LIU SS, WU X, ZHOU SY, et al.Establishment and preliminary evaluation of alloxan diabetic models with three mouse strains[J]. Chin J Pharm Anal, 2015, 35(11):1958
[4] NEUMILLER JJ, LINDY W, KEITH CR.Dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus[J]. Pharmacotherapy, 2010, 30(5):463
[5] BANERJEE M, YOUNIS N, SORAN H.Vildagliptin in clinical practice:a review of literature[J].Expert Opin Pharmacother, 2009, 10(16):2745
[6] NATHAN DM, BUSE JB, DAVIDSON MB, et al.Medical management of hyperglycemia in type 2 diabetes:a consensus algorithm for the initiation and adjustment of therapy[J].Diabetes Care, 2009, 32(8):193
[7] KENDALL DM, CUDDIHY RM, BERGENSTAL RM.Clinical application of incretin-based therapy:therapeutic potential, patient selection and clinical use[J].Eur J Intern Med, 2009, 20(Suppl 2):S329
[8] PALALAU AI, TAHRANI AA, PIYA MK, et al.DPP-4 inhibitors in clinical practice[J].Postgrad Med, 2009, 121(6):70
[9] MATHIEU C.The scientific evidence:vildagliptin and the benefits of islet enhancement[J].Diabetes Obes Metab, 2009, 11 (Suppl 2):9
[10] KEATING GM.Vildagliptin:a review of its use in type 2 diabetes mellitus[J].Drugs, 2014, 74(5):587
[11] 卢林林, 王养维.糖尿病药物治疗新靶点—维格列汀[J].医学研究杂志, 2014(4):179 LU LL, WANG YW.Vildagliptin:a new target for the treatment of type 2 diabetes mellitus[J].J Med Res, 2014(4):179
[12] SHANTIKUMAR S, SATHEESHKUMAR N, R.Pharmacokinetic and protein binding profile of peptidomimetic DPP-4 inhibitor- Teneligliptin in rats using liquid chromatography-tandem mass spectrometry[J].J Chromatogr B, 2015, 1002:194
[13] 杨倩, 袁雯玮.超高效液相色谱法测定盐酸博来霉素的有关物质[J].药物分析杂志, 2015, 35(4):679 YANG Q, YUAN WW.UPLC determination of related substances in bleomycin hydrochloride[J].Chin J Pharm Anal, 2015, 35 (4):679