DEVELOPMENT AND VALIDATION OF A GAS CHROMATOGRAPHY-MASS SPECTROMETRY WITH SELECTED ION MONITORING METHOD FOR THE DETERMINATION OF TRACE LEVELS OF METHANE SULFONYL CHLORIDE AS AN IMPURITY IN ITRACONAZOLE ACTIVE PHARMACEUTICAL INGREDIENT
Abstract
ABSTRACT
Objective: To develop an accurate, precise, and linear gas chromatographic-mass spectrometry selective ion monitoring (SIM) method for quantitative
estimation of methane sulfonyl chloride (MSC) as an impurity in itraconazole (ICR) active pharmaceutical ingredient (API) at ppm level and validated
as per International Council of Harmonization (ICH) guidelines.
Methods: This method used in SIM mode mass selective detection was developed and validated for the trace level analysis of an impurity.
Chromatographic separation of MSC was achieved in 5.45 minutes and m/z value was 79 on SIM mode, ZB-5 ms 30 m × 0.25 mm × 0.25 µm column,
using helium carrier gas with 1.0 ml/min.
Results: The method was linear for MSC in ICR 1.90-7.5 µg/ml, respectively. The coefficient of correlation (r
) for the MSC was better than 0.999. The
limit of detection and limit of quantification (LOQ) obtained were 0.44 and 1.32 µg/ml. The method was fully validated, complying Food and Drug
Administration, ICH, and European Medicines Agency guidelines. Furthermore, verified precision, accuracy, LOQ precision, LOQ accuracy, ruggedness,
and robustness.
2
Conclusion: The methods were successfully validated to determination and quantification of MSC in ICR API. Hence, the method holds good for the
routine trace analysis of MSC in ICR and various pharmaceutical industries as well as academics.
Keywords: Methane sulfonyl chloride, Itraconazole, Gas chromatography-mass spectrometry, Method development, Method validation.
Downloads
References
REFERENCES
Verenitch SS, Lowe CJ, Mazumder A. Determination of acidic drugs
and caffeine in municipal wastewaters and receiving waters by gas
chromatography-ion trap tandem mass spectrometry. J Chromatogr A
;1116(1-2):193-203.
Available from: https://www.en.wikipedia.org/wiki/Gas_
chromatography%E2%80%93 mass_spectrometry.
Available from: http://www.sge.com/
uploads/55/6a/556ae4e55c042c95832191d30557f017/TA-0061-C.pdf.
The European Agency for the Evaluation of Medicinal Products,
ICH Topic S1B, Note for Guidance on Carcinogenicity: Testing for
Carcinogenicity of Pharmaceuticals; 1998.
European Medicines Agency, Evaluation of Medicines for Human Use,
Guideline on the Limits of Genotoxic Impurities; 2007.
Dileep Kumar M. Analysis of Genotoxic Impurities in API’s in
Compliance with ICH Guidelines using Gas Chromatography Mass
Spectrometry. Waltham, United States: Centre of Excellence for
Analytical Sciences Perkin Elmer (India.) Pvt., Ltd.
Zhao L, Quimby B. Analysis of Drugs by using the Ultra Inert Inlet.
Liners with Wool. Wilmington, DE, USA: Agilent Technologies, Inc.
Bari SB, Kadam BR, Jaiswal YS, Shirkhedkar AA. Impurity profile:
Significance in active pharmaceutical ingredient. Eurasian J Anal Chem
;2(1):33-53.
Veenaeesh P, Manikumar G, Manjusha. P, Padmasri A. Determination
of methyl methane sulfonate, ethyl methane sulfonate and isopropyl
methane sulfonate impurities in Lopinavir API by GC/MS/MS using
electron ionization. Int J Pharm Res Rev 2014; 3(2):11-6.
Kashif UL, Kumar N. Validation of LC-MS/MS method for the
simultaneous estimation of Itraconazole and its metabolite hydroxyl
Itraconazole in plasma. Asian J Pharm Clin Res 2014;7 Suppl 1:131-6.
Geneva .The Impact of Implementation of ICH Guidelines in Non ICH
Countries. English Distribution General 2001; 1-29.
United States Pharmacopoeia (USP). 2006. p. 1577-8.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.