Rationality Evaluation of Packaging Materials and Study on Impurity Profiling of Cilnidipine Preparations by HPLC-Q-TOF/MS

Author(s): Hongxia Zeng, Jian Wang*, Bingqi Zhu, Peng Shao, Weihui Zhong

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 2 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: The rationality of cilnidipine tablets and capsules with four different pharmaceutical packaging materials was evaluated, and the structure of photodegradation impurities was analyzed by LC-Q-TOF.

Materials and Methods: The impurity profiling of commercial cilnidipine tablets and capsules was analyzed by LC-Q-TOF for the further improvement of official monograph in pharmacopoeias and the source of the impurities was investigated. The contents of photodegradation impurities were analyzed by HPLC, and remarkable difference in the formation of the photodegradation impurities in cilnidipine tablets and capsules with four different pharmaceutical packaging materials was observed. The shading effect of the four packaging materials was investigated by UV-Vis spectrophotometer and a remarkable difference was detected, which might be responsible for the difference in the formation of photodegradation products. The structures of photodegradation products were further characterized by LC-Q-TOF MS/MS. Five impurities in commercial cilnidipine tablets and capsules were separated and identified based on the high resolution MS/MS data.

Results: The obtained results revealed that the impurity III was derived from the ethanol solution of cilnidipine when it was exposed to light, and the impurity II was produced when the cilnidipine powder was exposed to light directly. The concentrations for 50% reduction of impurity II and impurity III on the Chinese hamster lung cells (CHL) with CellTiter-Glo method were studied and the results indicated that the cytotoxicity of impurity II and impurity III on CHL cells was larger than cytotoxicity of cilnidipine.

Conclusion: On the basis of our study, we suggested that the pharmaceutical packaging materials of cilnidipine tablets should be modified.

Keywords: Photodegradation impurities, cilnidipine, pharmaceutical packaging materials, LC-Q-TOF mass spectrometry, source, cytotoxicity.

[1]
Takahara, A.; Uchida, H.; Konda, T.; Dohmoto, H.; Yoshimoto, R.; Komori, M.; Morioka, T.; Ono, I.; Takata, Y.; Kato, H. Antihypertensive effects of repeated oral administration of cilnidipine, a novel calcium antagonist, in 2K1C renal hypertensive dogs. Folia. Pharm. Japonica., 1995, 106(4), 279-287.
[2]
AlOthman, Z.A.; Rahman, N.; Siddiqui, M.R. Review on pharmaceutical impurities stability studies and degradation products. Rev. Adv. Sci. Eng, 2013, 2, 155-166.
[3]
Ling-Yu, H.E.; Gao-Yun, H.U.; Zhou, Y.B.; Liu, J.H. Determination of Cilnidipine and its related substances by RP-HPLC. West China J. Pharm. Sci., 2004, 19(1), 70-71.
[4]
Wang, S.G.; Pan, G.U. Determination of cilnidipine related substances by RP-HPLC. Anhui Med. Pharm. J., 2011, 10, 1224-1226.
[5]
Zhu, P.; Ding, L.; He, J.; Zheng, G. Rapid characterization of impurities in the bulk drug of nifedipine by high performance liquid chromatography-quadrupole time of fight mass spectrometry. Chin. J. Chromatogr.,, 2012, 30(10), 1026-1030.
[6]
Zhao, X.; Li, B.; Chen, B.; Wang, S. Identification and quantification of impurities in amlodipine besylate tablets. Acta. Universitatis. Med. NanJing. (Natural Science), 2013, 33(9), 1314-1317.
[7]
Zhang, N.; Yu, L.J.; Li, J.; Tong, J.W.; Meng, J.Q.; Zhang, M.; Shi, Y.Q. Analysis and evaluation of the impurity of felodipine and its tablets. Acta Pharm. Sinica., 2012, 47(2), 223-228.
[8]
Zhu, P.X.; Chen, J.J.; Lin, L.H.; Zhou, M.H. Characterization of impurities in nitrendipine bulk drug by liquid chromatography/ion trap mass spectrometry. Chin. J. Pharm. Anal., 2012, 32(1), 88-91.
[9]
Sudhakar, P.; Nirmala, M.; Moses Babu, J.; Vyas, K. Ganta Madhusudan Reddy, Vijaya Bhaskar, B.; Pratap Reddy, P.; Mukkanti, K. Identification and characterization of potential impurities of amlodipine maleate. J. Pharm. Biomed. Anal., 2006, 40(3), 605-613.
[10]
Zeng, H.; Wang, F.; Zhu, B.; Zhong, W.; Shan, W.; Wang, J. Study of the structures of photodegradation impurities and pathways of photodegradation of cilnidipine by liquid chromatography/Q-Orbitrap mass spectrometry. Rapid Commun. Mass Spectrom., 2016, 30(15), 1771-1778.
[11]
Siddiqui, M.R.; AlOthman, Z.A.; Rahman, N. Analytical techniques in pharmaceutical analysis: a review. Arab. J. Chem., 2017, 10, 1409-1421.
[12]
Rahman, N.; Azmi, S.N.H.; Wu, H.F. The importance of impurity analysis in pharmaceutical products: an integrated approach. Accredit. Qual. Assur., 2006, 11, 69-74.
[13]
Luis, J. Núñez-Vergara, Carlos Sunkel, Squella, J. A. Photodecomposition of a new 1, 4-dihydropyridine: furnidipine. J. Pharm. Sci., 1994, 83(4), 502-507.
[14]
Li, R.; Wang, F.; Chen, L.; Zhu, S.; Wu, L.; Jiang, S.; Xu, Q.; Zhu, D. Stability of an anti-stroke peptide: driving forces and kinetics in chemical degradation. Int. J. Pharm., 2014, 472(1-2), 148-155.
[15]
Law, S.L.; Lo, W.Y.; Lin, F.M.; Chaing, C.H. Dissolution and absorption of nifedipine in polyethylene glycol solid dispersion containing phosphatidylcholine. Int. J. Pharm., 1992, 84(2), 161-166.
[16]
Bratin, K.; Kissinger, P.T. Glassy-carbon amperometric transducers as electrochemical detectors in liquid chromatography The influence of oxygen. Talanta, 1982, 29(5), 365-370.
[17]
Zanocco, A.L.; Diaz, L.; Lopez, M.; Nunez-Vergara, L.J.; Squella, J.A. Polarographic study of the photodecomposition of nimodipine. J. Pharm. Sci., 1992, 81(9), 920-924.
[18]
Lei, Y. M.; Ding, J. S.; Zhang, B. K.; Cheng, Z. N.; Li, H. D. Stability of cilnidipine in light. Central South. Pharm.,, 2003, 1, 011-013.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 2
Year: 2020
Published on: 23 January, 2020
Page: [220 - 230]
Pages: 11
DOI: 10.2174/1573412914666180517100626
Price: $65

Article Metrics

PDF: 19
HTML: 3
EPUB: 1
PRC: 1