HPLC法测定盐酸西那卡塞原料药有关物质

目的：建立高效液相色谱法测定盐酸西那卡塞原料药的有关物质。方法：采用Venusil XBP-C₁₈色谱柱（4.6 mm×150 mm，5 μm），以含0.5%三乙胺的30 mmol·L^-1磷酸二氢钾水溶液（磷酸调pH 2.5）-甲醇-乙腈-异丙醇（60∶15∶15∶10）为流动相等度洗脱，流速为1.3 mL·min^-1，柱温为35℃，检测波长为220 nm。结果：盐酸西那卡塞与各杂质峰之间的分离度良好，10个已知杂质在各自的线性范围内线性关系良好（r2>0.999，n=6）；3批盐酸西那卡塞样品测定结果显示，已知杂质及最大未知单杂均小于0.1%，杂质总含量小于0.5%。结论：经方法学验证，本法灵敏度高，专属性好，可用于盐酸西那卡塞原料药有关物质的测定。

Objective:To establish an HPLC method for the determination of related substances in cinacalcet hydrochlorid raw material.Methods:HPLC was adopted on a Venusil XBP-C₁₈ column (4.6 mm×150 mm, 5 μm)with the mobile phase of 30 mmol·L^-1 potassium dihydrogen phosphate solution containing 0.5% triethylamine (pH was adjusted to 2.5 with phosphate acid)-methanol-acetonitrile-isopropanol (60:15:15:10).The flow rate was 1.3 mL·min^-1,and the column temperature was maintained at 35℃,the detection wavelength was set at 220 nm.Results:The resolutions between cinacalcet hydrochlorid and known impurities were greater than those of the requirements.The calibration curves of 10 known impurities were linear in the self-concentration range (r²>0.999,n=6).The determination results of the three batches of cinacalcet hydrochlorid samples showed that the known impurities were less than 0.1%,the maximum single unknown impurity was less than 0.1%,and the total impurities were less than 0.5%.Conclusion:The method showed good sensitivity and specificity,and it is suitable for the quality control of cinacalcet hydrochlorid.

[1] IQBAL J,ZAIDI M,SCHNEIDER AE.Cinacalcet hydrochloride(Amgen)[J].Drugs,2003,6(6):587
[2] BARMAN BJ,SCOTT LJ.Cinacalcet hydrochloride[J].Drugs,2005,65(2):271
[3] 谭秀艳,张敏敏,李中东,等.盐酸西那卡塞在治疗甲状旁腺功能亢进中的研究进展[J].中国医院药学杂志,2017,37(2):185 TAN XY,ZHANG MM,LI ZD,et al.Research progress in cinacalcet hydrochloride against hyperparathyroidism[J].Chin Hosp Pharm J,2017,37(2):185
[4] NIROGI R,KANDIKERE V,KOMARNENI P,et al.Quantification of cinacalcet by LC-MS/MS using liquid-liquid extraction from 50μL of plasma[J].J Pharm Biomed Anal,2011,56(2):373
[5] YANG F,WANG HY,ZHAO Q,et al.Determination of cinacalcet hydrochloride in human plasma by liquid chromatography-tandem mass spectrometry[J].J Pharm Biomed Anal,2012,61:237
[6] 赵玲,赵春才,陆超,等.HPLC法测定盐酸西那卡塞片含量[J].中国药房,2014,25(13):1216 ZHAO L,ZHAO CC,LU C,et al.Content determination of cinacalcet hydrochloride tablets by HPLC[J].China Pharm,2014,25(13):1216
[7] 朱建喜,庄波阳,曾凡湘,等.HPLC测定盐酸西那卡塞有关物质[J].中国现代应用药学,2015,32(2):185 ZHU JX,ZHUANG BY,ZENG FX,et al.Determination of the related substances of cinacalcet hydrochloride by HPLC[J].Chin J Mod Appl Pharm,2015,32(2):185
[8] THIEL OR,BERNARD C,TORMOS W,et al.Practical synthesis of the calcimimetic agent,cinacalcet[J].Tetrahedron Lett,2008,49(1):13
[9] 胡键,董菁,施小新.盐酸西那卡塞的合成[J].中国医药工业杂志,2010,41(7):488 HU J,DONG J,SHI XX.Synthesis of cinacalcet hydrochloride[J].Chin J Pharm,2010,41(7):488
[10] 李林羚,胡雪峰,杨玉雷,等.盐酸西那卡塞的工艺研究[J].中国新药杂志,2013,22(7):834 LI LL,HU XF,YANG YL,et al.Synthesis process of cinacalcet hydrochloride[J].Chin J New Drugs,2013,22(7):834
[11] PREDIGER P,SILVA AR,CORREIA CRD.Construction of 3-arylpropylamines using Heck arylations.The total synthesis of cinacalcet hydrochloride,alverine,and tolpropamine[J].Tetrahedron,2014,70(20):3333
[12] GOOODMAN CA,JANCI EM,ONWODI O,et al.A two-step,one pot preparation of amines via acyl succinimides.Synthesis of the calcimimetic agents cinacalcet,NPS R-467,and NPS R-568[J].Tetrahedron Lett,2015,56(44):4468
[13] 中华人民共和国药典2015年版.四部[S].2015:374 ChP 2015.Vol Ⅳ[S].2015:374
[14] Guidance for Industry:Analytical Procedures and Methods Validation for Drugs and Biologics[EB/OL].1987[2015-01-18].http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm386366.pdf
[15] Guidance on Validation of Analytical Procedures:Text and Methodology[EB/OL].2003[2015-01-18].http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002662.pdf
[16] 许明哲,黄宝斌,杨青云,等.分析方法验证、转移和确认概念解析[J].药物分析杂志,2015,35(1):169 XU MZ,HUANG BB,YANG QY,et al.Elaboration on the concepts of analytical method validation,transfer and verification[J].Chin J Pharm Anal,2015,35(1):169
[17] 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