Studies on related substances in cinacalcet hydrochloride by LC-MS

HU Zhongfang; SONG Min; HANG Taijun

doi:10.11665/j.issn.1000-5048.20160615

Journal of China Pharmaceutical University > 2016 > 47(6): 719-726. > DOI: 10.11665/j.issn.1000-5048.20160615

HU Zhongfang, SONG Min, HANG Taijun. Studies on related substances in cinacalcet hydrochloride by LC-MS[J]. Journal of China Pharmaceutical University, 2016, 47(6): 719-726. DOI: 10.11665/j.issn.1000-5048.20160615

Citation:

PDF (1139 KB)

Studies on related substances in cinacalcet hydrochloride by LC-MS

More Information

Graphical Abstract

Abstract

Abstract

To develop an LC-MS method for the separation and identification of the related substances in cinacalcet hydrochloride. The separation was carried out on a Thermo BDS Hypersil C₁₈ column(100 mm×4. 6 mm, 2. 4 μm)with mobile phase consisting of 0. 1% ammonium acetate buffer-acetonitrile(93∶7)(A)and acetonitrile(B)by gradient elution. The related substances were identified by electrospray positive ionization high resolution TOF/MS and MS/MS, and verified further through reference substances. Cinacalcet hydrochloride and itsrelated substances were separated under the established LC-MS condition. Ten related substances were detected and identified to be one starting material, one intermediate, four synthetic by-products and five degradation products. It showed that the LC-MS method was useful for separating and identifying the related substances in cinacalcet hydrochloride. And the results obtained are valuable for cinacalcet hydrochloride manufacturing process control and quality assurance.
- cinacalcet hydrochloride,
- related substance,
- structure identification,
- LC-MS

FullText(HTML)

References (14)

References

[1]	Dong BJ.Cinacalcet:an oral calcimimetic agent for the management of hyperparathyroidism[J].Clin Ther,2005,27(11):1725-1751.
[2]	Sajid-Crockett S, Singer FR, Hershman JM. Cinacalcet for the treatment of primary hyperparathyroidism[J].Metabolism,2008,57(4):517-521.
[3]	Martín AA,Villalón AA,Ramírez ML,et al.Low-dose cinacalcet reduces serum calcium in patients with primary hyperparathyroidism not eligible for surgery[J].Endocrinol Nutr,2011,58(1):24-31.
[4]	Somnay YR, Weinlander E, Schneider DF, et al. The effect of cinacalcet on intraoperative findings in tertiary hyperparathyroidism patients undergoing parathyroidectomy[J].Surgery,2014,156(6):1308-1314.
[5]	Nirogi R, Kandikere V, Komarneni P, et al. Quantification of cinacalcet by LC-MS/MS using liquid-liquid extraction from 50 μL of plasma[J].J Pharm Biomed Anal,2011,56(2):373-381.
[6]	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,2012,61:237-241.
[7]	Zhao L,Zhao CC,Lu C,et al.Content determination of cinacalcet hydrochloride tablets by HPLC[J].J China Pharm(中国药房),2014,25(13):1216-1217.
[8]	Zhu JX,Zhuang BY,Zeng FX,et al.Determination of the related substances of cinacalcet hydrochloride by HPLC[J].Chin J Mod Appl Pharm(中国现代应用药学),2015,32(2):185-189.
[9]	Thiel OR,Bernard C,Tormos W,et al.Practical synthesis of the calcimimetic agent,cinacalcet[J].Tetrahedron Lett,2008,49(1):13-15.
[10]	Hu J,Dong J,Shi XX.Synthesis of cinacalcet hydrochloride[J].Chin J Pharm(中国医药工业杂志),2010,41(7):488-490.
[11]	Li LL,Hu XF,Yang YL,et al.Synthesis process of cinacalcet hydrochloride[J].Chin New Drugs J(中国新药杂志),2013,22(7):834-836.
[12]	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):3333-3341.
[13]	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):4468-4471.
[14]	Chen LL,Song M,Zhang G,et al. Identification of related substances in ambrisentan by LC-MS/MS[J].J China Pharm Univ(中国药科大学学报),2016,47(1):58-65.

Cited By

Get Citation

PDF

XML

Article views (903) PDF downloads (1517)

Turn off MathJax

Article Contents

Abstract

References

Studies on related substances in cinacalcet hydrochloride by LC-MS

Abstract

References

Catalog

Export File

Citation

Format

Content