DETERMINATION OF RESIDUAL DIMETHYL SULFATE IN METHOXSALEN DRUG SUBSTANCE BY PRE-COLUMN DERIVATIZATION WITH STATIC HEADSPACE GAS CHROMATOGRAPHY
Objective: Dimethyl sulfate has been highlighted as potential genotoxic and carcinogenic impurity. A sensitive Headspace gas chromatography (HS-GC) method with pre-column derivatization was developed and validated for the determination of dimethyl sulfate impurity in methoxsalen active pharmaceutical ingredient.
Methods: HS-GC method on the column Agilent DB-5, 30m X 0.53 mm, film thickness 1.5 Âµm, with flame ionization detector (FID) was used. Derivatization reagent concentration, time of reaction and pH of the solution were optimized during method development. This analytical method was evaluated by performing method validation as per ICH guideline.
Results: The proposed method was specific, linear, accurate, rugged and precise. The calibration curves showed good linearity over the concentration range of 0.5 Î¼g/ml to 3.0 Î¼g/ml and the correlation coefficient was 0.999. Method had very low limit of detection (LOD) and limit of quantification (LOQ) 2.0 Î¼g/g and 5.0 Î¼g/g respectively. Accuracy was observed within 98.1%â€“104.5%.
Conclusion: The developed method was demonstrated to be accurate, robust and sensitive for the determination of dimethyl sulfate impurity in methoxsalen drug substance.
2. United State Pharmacopoeia. Methoxsalen official monograph. USP 40; 2016. p. 5087-8.
3. Shenoi S, Prabhu S. Photochemotherapy (PUVA) in psoriasis and vitiligo. Indian J Derm Vene Leprol 2014;80:497-504.
4. Parrish J, Fitzpatrick T, Tanenbaum L, Pathak M. Photochemotherapy of psoriasis with oral methoxsalen and longwave ultraviolet light. New Engl J Med 1974;291:1207 11.
5. Melski J, Tanenbaum L, Parrish J, Fitzpatrick T, Bleich H. Oral methoxsalen photochemo therapy for the treatment of psoriasis: a cooperative clinical trial. J Invest Derm 1977;68:328 35.
6. IARC. Some pharmaceutical drugs. IARC Monogr Eval Carcinog Risk Chem Hum 1980;24:1â€“337.
7. IARC. Genetic and related effects. An updating of selected IARC monographs from Volumes 1 to 42. IARC Monogr Eval Carcinog Risks Hum Suppl 1987;6b:1â€“729.
8. IARC. Overall evaluations of carcinogenicity. An updating of IARC Monographs volumes 1 to 42. IARC Monogr Eval Carcinog Risks Hum Suppl. 1987;7a:1â€“440.
9. ICH. M7(R1) Addendum to ICH M7. Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk; Application of the Principles of the ICH M7 Guidance to Calculation of Compound-Specific Acceptable Intakes. ICH Harmon Guid; 2017.
10. ICH. Impurities in new drug substances Q3A (R2); 2006.
11. FDA. U. S. Dept of Health and Human Services Food and Drug Adm. Guidance for Industry ANDAs: Impurities in Drug Substances; 2009.
12. Drugs. com. Methoxsalen dosage; 2016. Available from: https://www.drugs.com/dosage/methoxsalen.html. [Last accessed on 01 May 2018].
13. NIOSH. Manual of Analytical Methods (NMAM). Fourth Edition. DIMETHYL SULFATE. METHOD 2524; 1994. Available from: https://www.cdc.gov/niosh/docs/2003-154/pdfs/2524.pdf. [Last accessed on 01 May 2018]
14. FEAIIG. Federation of the Employment Accidents Insurance Institutions of Germany. Centre for Accident Prevention and Occu Med. Method for the determination of dimethyl sulfate (DMS). Ana Met Air Monit Met 1997;5:75-105. Available from: http://onlinelibrary.wiley.com/doi/10.1002/3527600418.am7778e0005/pdf. [Last accessed on 01 May 2018]
15. Prabhu P. Trace level determination of residues of dimethyl sulfate and diethyl sulfate in pharmaceutical products by headspace gas chromatography and mass spectrometry following derivatization with pentafluorobenzenethiol. Experimental Notes Perkin Elmer; 2015. Available from: http://www.perkinelmer.com/ CMSRe-sources/Images/20130104_8-Trace-level-determination-residues of dimethyl sulfate.pdf. [Last accessed on 01 May 2018]
16. Zheng J, Wayne A, Zhang S, Wittenberger S. Determination of low ppm levels of dimethyl sulfate in an aqueous soluble API intermediate using liquidâ€“liquid extraction and GCâ€“MS. J Pharma Biomed Anal 2009;50:1054-9.
17. Nalavade A, Sandhyakumari B, Ramakrishna K, Srinivasarao V. Development and evaluation of class-1 solvent 1, 2-dichloroethane and dimethyl sulphate as a genotoxic impurity in sildenafil citrate drug substance by using GC-MS technique. Int J Pharm Pharma Sci 2014;6;552-5.
18. SchÃ¤fer C, ZÃ¶llner P. Determination of trace levels of dimethyl sulfate in the presence of monomethyl sulfate by gas chromatography-mass spectrometry. J Chrom A 2013;4:10.
19. Rahman M, Gullick D, Hoerner J, Bartlett M. Determination of genotoxic impurities monomethyl sulfate and dimethyl sulfate in active pharmaceutical ingredients. Anal Methods 2017;7:1112-8.
20. Nanduri V, Reddy K, Adapa V, Ramakrishna K. Validated chromatographic methods for the determination of process related toxic impurities in pantoprazole sodium. Chromatographia 2008;68:481â€“4.
21. Narendrakumar M, Krishna Reddy V, Sharma H, Kaleemullah T, Madhava Reddy P, John P, et al. Simple and sensitive ion chromatography method for the simultaneous determination of dimethyl sulfate and diethyl sulfate contents in metoprolol tartrate drug substance. Chem Sin 2011;2:164-72.
22. ICH. Validation of analytical procedures: Text and methodology Q2 (R1); 2005.
23. Hiers G, Hager F. Anisole. Org Syn 1941;1;58;9;1929;12. Doi:10.15227/orgsyn.009.0012
24. Lunn G, Sansone E. Validation of techniques for the destruction of dimethyl sulfate. Am Indu Hyg Assoc J 1985;46:111-4.