Open Access Open Access  Restricted Access Subscription Access

Development of a Highly Sensitive Method for Quantitative Estimation of Dimethyl Sulfate Impurity in Neostigmine Methylsulfate Drug substances by Using GC-MS

Amit Gosar, Amit Joglekar, Tabrez Shaikh, Sandeep Mhatre, Swapnil Patil

Abstract


A selective and highly sensitive gas chromatography-mass spectrometry (GC-MS) method was developed for the determination of Dimethyl Sulfate (DMS) impurity in Neostigmine Methylsulfate drug substance. The method was validated as per International Council for Harmonisation (ICH) guidelines, for which limit of detection and limit of quantitation obtained were 25.48 ppm and 77.20 ppm, respectively. The regression coefficient found for the linearity study was 0.9986. The recovery of the spiked Dimethyl Sulfate in drug substance obtained was in the range of 84.40% to 88.24% ensured the accuracy of the method The method precision with relative standard deviation (RSD) for repeatability and intermediate precision was less than 5%. The method can be adapted to determine Dimethyl Sulfate in Neostigmine Methylsulfate drug substance (API).


Full Text:

PDF

References


M. B. Walker (1935), “Case showing the effect of prostigmin on myasthenia gravis”, Proceedings of the Royal Society of Medicine, Volume 28, Issue 6, pp. 759–761.

R. N. Banerjee, A. L. Sahni, K. A. Chacko, K. Vijay (1972), “Neostigmine in the treatment of Elapidae bites”, The Journal of the Association of Physicians of India, Volume 20, Issue 7, pp. 503–509.

G. S. Murphy, J. W. Szokol, J. S. Vender, J. H. Marymont, M. J. Avram (2002), “The use of neuromuscular blocking drugs in adult cardiac surgery: results of a national postal survey,” Anesthesia and Analgesia, Volume 95, Issue 6, pp. 1534–1539.

M. M. Mehndiratta, S. Pandey, T. Kuntzer (2011), “Acetyl cholinesterase inhibitor treatment for myasthenia gravis”, Cochrane Database of Systematic Reviews, Volume 2, Article ID CD006986

Selva M, Perosa A. (2008), “Green chemistry metrics: a comparative evaluation of dimethyl carbonate, methyl iodide, dimethyl sulfate and methanol as methylating agents”, Green Chemistry, Volume 10, Issue 4, pp. 457−464.

Jarrahpour A, Zarei M. (Apr 8, 2009), “DMF-dimethyl sulfate as a new reagent for the synthesis of β-lactams”, Tetrahedron Letters, Volume 50, Issue 14, pp. 1568−1570.

Zheng J, Pritts WA, Zhang S, Wittenberger S. (Dec 5, 2009), “Determination of low ppm levels of dimethyl sulfate in an aqueous soluble API intermediate using liquid–liquid extraction and GC–MS”, Journal of pharmaceutical and biomedical analysis, Volume 50, Issue 5, pp. 1054−1059.

Gilland JC, Bright AP. (Jun 1, 1980), “Determination of dimethyl and diethyl sulfate in air by gas chromatography”, American Industrial Hygiene Association Journal, Volume 41, Issue 6, pp. 459−462.

Khan M, Jayasree K, Reddy KK, Dubey PK (Jan 25, 2012), “A validated CE method for determining dimethylsulfate a carcinogen and chloroacetyl chloride a potential genotoxin at trace levels in drug substances”, Journal of pharmaceutical and biomedical analysis, Volume 58, pp. 27−33.

Guideline (2014), “ICH Harmonized Tripartite. Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic RISK M7”, International conference on harmonization of technical requirements for registration of pharmaceuticals for human use (ICH): Geneva.

Snodin DJ, McCrossen SD. (Jul 1, 2012), “Guidelines and pharmacopoeial standards for pharmaceutical impurities: overview and critical assessment”, Regulatory Toxicology and Pharmacology, Volume 63, Issue 2, pp. 298−312.

Chan CC, Lee YC, Lam H, Zhang XM (Apr 23, 2004), “Analytical method validation and instrument performance verification”, John Wiley & Sons,

Guideline IH (Nov 2005), “Validation of analytical procedures: text and methodology Q2 (R1)”, International conference on harmonization, Geneva, Switzerland, pp. 11−12.


Refbacks