DETERMINATION OF TRACEABLE GENOTOXIC IMPURITY CHLOROACETYL CHLORIDE A CARCINOGEN BY LC/MS/MS IN DRUG SUBSTANCES
Abstract
ABSTRACT
Objective: A simple liquid chromatography-mass spectroscopy/mass spectroscopy (LC/MS/MS) method was developed for determining chloroacetyl
chloride (CAC), which is possible genotoxic impurity at trace levels in pharmaceutical drug substances.
Methods: The suitable LC/MS/MS compatible buffers acetonitrile and ammonium format were used to avoid matrix interferences and for better
detectability. This method eliminates the solvent extraction and derivatization steps and requires only the direct injection of the sample into the
LC/MS.
Results: The method is specific, accurate, and critical validation parameters have been done and established the limit of quantitation level of
0.003 µg/g.
Conclusion: The method possesses the lowest detection level when compared with other methods referred in this journal.
Keywords: Liquid chromatography-mass spectroscopy, Chloroacetyl chloride, Active pharmaceutical ingredients, Carcinogenic, Drug substance.
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References
REFERENCES
International Conference on Harmonisation of Technical Requirements
for Registration of Pharmaceuticals for Human Use. ICH Q3A(R2);
International Conference on Harmonisation of Technical Requirements
for Registration of Pharmaceuticals for Human Use. ICH Q3B(R2);2006.
Guideline on the Limits of Genotoxic Impurities, European Medicines
Agency. EMEA/CHMP, 2011.
Khan M, Jayasree K, Reddy KV, Dubey PK. A validated CE method for
determining dimethylsulfate a carcinogen and chloroacetyl chloride a
potential genotoxin at trace levels in drug substances. J Pharm Biomed
Anal 2012;58:27-33.
Analysis of Halo Acetic Acid in Tape Water Using LC/MS/MS (LC/
MS-8030) by Shimadzu Application News, No. C88, LAAN-A-LM
E059.
Chen CY, Chang SN, Wang GS. Determination of ten haloacetic acids
in drinking water using high-performance and ultra-performance
liquid chromatography-tandem mass spectrometry. J Chromatogr Sci
;47(1):67-74.
Zhanpen WU, Cody RB. Analytical Instrument Division. JEOL USA,
Inc.; 2004. Available from: http://www.jeol.com.
Domino MM, Pepich BV, Munch DJ, Fair PS, Xie Y, Munch JW,
et al. Determination of Haloacetic Acid and Dalopon in Drinking
Water by Liquid – Liquid Micro Extraction, Derivatization and Gas
Chromatography with Electron Capture Detector, EPA 815-B-03-002,
Haward GG. Determination of halogenated acetic acids by Ion
chromatography. US Army Biomedical Research & Development
Laboratory, Fort Detrick, Fredrick, 1991, MD21702-5010.
Xinlin Z, Mingli Y, Lina L, Qun X, Rohrer J. Determination of
monochloro acetic acid in carbocisteine, Thermofisher Scientific,
Shangai, Peoples republic of China, Thermofischer Scientific,
Sunnyvale, CA, USA. Application Note 1076.
Yang Q, Haney BP, Vaux A, Riley DA, Heidrich L, He P, et al
Controlling the genotoxins. Organ Proc Res Dev 2009;13:786-91.
Elder DP, Lipczynski AM, Teasdale A. Control and analysis of alkyl
and benzyl halides and other related reactive organohalides as potential
genotoxic impurities in active pharmaceutical ingredients (APIs).
J Pharm Biomed Anal 2008;48:497-507.
Elder DP, Snodin D, Teasdale A. Analytical approaches for the detection
of epoxides and hydroperoxides in active pharmaceutical ingredients,
drug products and herbals. J Pharm Biomed Anal 2010;51(5):1015-23.
International Conference on Harmonization of Technical Requirements
for Registration of Pharmaceuticals for Human Use, Guideline
Validation of Analytical Procedure Text and Methodology 1997, Q2
B(R1).
Validation of Compendial Proceedings. USP38/NF33; 2015.
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