Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Back
Research Article

Characterization of an Unknown Impurity in Indobufen Tablets by HPLC-Q-TOF MS and NMR

Author(s): Yu Li, Xiangwen Kong, Liya Hong*, Chen Yue, Xinyue Wang and Peixi Zhu*

Volume 17, Issue 7, 2021

Published on: 16 June, 2020

Page: [885 - 891] Pages: 7

DOI: 10.2174/1573412916999200616124632

Price: $65

Abstract

Background: Indobufen is a drug that hinders the aggregation of platelets by reversibly repressing the cyclooxygenase enzyme, further bringing about diminished thromboxane production. During quality control of indobufen tablets, an unknown impurity was detected.

Objective: To characterize an unknown impurity in indobufen tablets.

Methods: A new method compatible with mass spectrometry detection was set up. A C18 column at 35 °C with a mobile phase consisting of aqueous buffer (including ammonium formate) and methanol (35: 65, v/v) was used at a flow rate of 1.0 mL/min at 228 nm. High-performance liquid chromatography quadrupole time-of-flight mass spectrometry mass spectrometry (HPLC-Q-TOF MS) was used to identify the impurity with the electrospray ionization (ESI) source in the positive ionization mode.

Results: The results of HPLC-Q-TOF MS analysis indicated that the protonated molecule ions [M + H]+ of the unknown impurity was at m/z 312. Preparative LC method was put into practice with a Prep- C18 column with a mobile phase consisting of water and methanol (20: 80, v/v) at a flow rate of 20.0 mL/min at 228 nm. The assignment of the 1D and 2D NMR signals was performed for the unknown impurity. In addition, possible formation of the novel impurity was also studied.

Conclusion: An unknown impurity in indobufen tablets was characterized. The impurity was assigned as 2-(4-(1-hydroxy-3-oxoisoindolin-2-yl) phenyl) butanoic acid.

Keywords: Indobufen, unknown impurity, HPLC-Q-TOF mass spectrometry, nuclear magnetic resonance (NMR), preparative liquid chromatography, LC-MS.

« Previous Next »
Graphical Abstract

[1]
Główka, F.K. LC procedure with SPE for quantification of indobufen enantiomers: pharmacokinetic studies. J. Pharm. Biomed. Anal., 2000, 22(1), 93-100.
[http://dx.doi.org/10.1016/S0731-7085(99)00259-9] [PMID: 10727127]
[2]
Barillà, F.; Pulcinelli, F.M.; Mangieri, E. Clopidogrel plus indobufen in acute coronary syndrome patients with hypersensitivity to aspirin undergoing percutaneous coronary intervention. Platelets, 2013, 24(3), 183-188.
[http://dx.doi.org/10.3109/09537104.2012.686072] [PMID: 22646157]
[3]
Lee, J.Y.; Sung, K.C.; Choi, H.I. Comparison of aspirin and indobufen in healthy volunteers. Platelets, 2016, 27(2), 105-109.
[PMID: 26083594]
[4]
Wiseman, L.R.; Fitton, A.; Buckley, M.M. Indobufen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in cerebral, peripheral and coronary vascular disease. Drugs, 1992, 44(3), 445-464.
[http://dx.doi.org/10.2165/00003495-199244030-00009] [PMID: 1382938]
[5]
Główka, F.K.; Karaźniewicz, M. Resolution of indobufen enantiomers by capillary zone electrophoresis. Pharmacokinetic studies of human serum. J. Chromatogr. A, 2004, 1032(1-2), 219-225.
[http://dx.doi.org/10.1016/j.chroma.2003.10.056] [PMID: 15065799]
[6]
Rahman, N.; Azmi, S.N.H.; Wu, H. The importance of impurity analysis in pharmaceutical products: an integrated approach. Accredit. Qual. Assur., 2006, 11, 69-74.
[http://dx.doi.org/10.1007/s00769-006-0095-y]
[7]
AlOthman, Z.A.; Rahman, N.; Siddiqui, M.R. Review on pharmaceutical impurities, stability studies and degradation products: an analytical approach. Rev. Adv. Sci. Eng., 2013, 2, 155-166.
[http://dx.doi.org/10.1166/rase.2013.1039]
[8]
Siddiqui, M.R.; AlOthman, Z.A.; Rahman, N. Analytical techniques in pharmaceutical analysis: a review. Arab. J. Chem., 2017, 10, S1409-1421.
[http://dx.doi.org/10.1016/j.arabjc.2013.04.016]
[9]
Chinese National Drug Standards. Chinese Pharmacopoeia Commission, Beijing. 2008; 71: pp. 177-8.
[10]
International Council on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH Q3B (R2), Impurities in New Drug Products 2006; 1-16.
[11]
Wang, S.Q.; Liu, X.J.; Zheng, L.Y. Synthesis of (±) ethyl 2-[4-(1-OXO-2-isoindoliny1) pheny1] butyrate. J. Shenyang Pharm. Univ., 2001, 18, 98-99.
[12]
Gao, X.M.; Chen, Y.X.; Chen, W.X. Synthesis of anticoagulant indobufen. Carol. J. Pharm., 1989, 20, 486-487.
[13]
Zheng, G.X.; Wang, Q.F. Preparation of indobufen. Carol. J. Pharm., 1991, 22, 291-293.
[14]
Cao, D.S.; Han, T.; Zhou, H.J.; Yu, R. Method for preparing indobufen. CN106631974A , 2017.

Rights & Permissions Print Cite
Article Metrics
13
1
© 2024 Bentham Science Publishers | Privacy Policy