Development and Validation of Static HS-GC Method for the Determination and Quantification of Residual Solvents of Bromhexine Hydrochloride (BHX)
Home >
2013,
Vol. 1 No. 02 > Development and Validation of Static HS-GC Method for the Determination and Quantification of Residual Solvents of Bromhexine Hydrochloride (BHX)
Authors
- Prafull MathurAnalytical Development Laboratory, Research and Development Centre, Dr. Datsons Labs Ltd,K- 4/1, Additional MIDC, Mahad-402309, India
- Suvigya MathurAnalytical Development Laboratory, Research and Development Centre, Dr. Datsons Labs Ltd,K- 4/1, Additional MIDC, Mahad-402309, India
- Anand Kumar MishraAnalytical Development Laboratory, Research and Development Centre, Dr. Datsons Labs Ltd,K- 4/1, Additional MIDC, Mahad-402309, India
- Tanaji KunjirAnalytical Development Laboratory, Research and Development Centre, Dr. Datsons Labs Ltd,K- 4/1, Additional MIDC, Mahad-402309, India
Keywords
Residual solvents, Static Headspace Gas chromatography, Method Validation, Bromhexine hydrochloride, Active pharmaceutical ingredient (API)
Abstract
The determination of residual solvents in drug substances is the mandatory requirement by various health authorities in the world. There are no analytical methods available in the literature that can simultaneously separate and quantitate residual solvents in bromhexine hydrochloride (BHX) active pharmaceutical ingredient (API). This paper describes the development and validation of a simple, efficient, accurate, and robust static headspace gas chromatography method for the determination of residual solvents, namely methanol, ethanol, ethyl acetate, monochlorobenzene, and benzene, in BHXAPI. This new method has been demonstrated to be accurate, linear, precise, reproducible, specific, and robust for its intended purpose. The method gives very good sensitivities viz. detection limits for benzene is 0.4 ppm, ethyl acetate 2 ppm and for others solvents 5 ppm and precision (below 9.0 % RSD) for all solvents. The results of this evaluation strongly indicate that this method can be readily used to determine residual solvents in BHX.
References
- B’Hymer, C. (2003). Residual solvent testing: a review of gas-chromatographic and alternative techniques. Pharmaceutical Research, 20, 337-344. http://dx.doi.org/10.1023/A:1022693516409
- Camarasu, C.C, Mezei-Szuts, M. & Varga GB (1998), Residual solvents determination inpharmaceutical products by GC-HD and GC–MS-SPME. Journal of Pharmaceutical and Biomedical Analysis, 18, 623–638. http://dx.doi.org/10.1016/S0731-7085(98)00276-3
- Devotta, I., Badiger, M. V., Rajamohanan, P. R., Ganapathy, S. & Mashelkar, R, A. (1995). Unusual retardation and enhancement in polymer dissolution: role of disengagement dynamics; Chemical Engineering Science, 50, 2557–2569. http://dx.doi.org/10.1016/0009-2509(95)00103-C
- Guyot-Hermann, A, M. (1991). Residual solvents and manufacturing processes; STP Pharma Pratiques, 1. 258–266.
- Harmonised Tripartite Guideline on Impurities: Residual Solvents (Q3C) (1997). International Conference on Harminisation of Technical Requirements for Registrations of Pharmaceuticals for Human Use (ICH), Geneva. http://www.ich.org/products/guidelines/quality/ article/quality-guilines.html
- Harmonised Tripartite Guideline on Maintenance of Note for Guidance onImpurities: Residual Solvents (Q3C(M)) (2002) International Conference on Harminisationof Technical Requirements for Registrations of Pharmaceuticals for Human Use (ICH), Geneva. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002674.pdf
- Identification and Control of Residual Solvents (2.4.24) (2006). 6th ed., European Pharmacopoeia, Directorate for the Quality of Medicines of the Council of Europe, Strasbourg.
- Kolb, B. & Ettre, L.S. (1991). Theory and practice of multiple headspace extraction; Chromatographia 32, 505–513. http://dx.doi.org/10.1007/BF02327895
- Laus, G., Andre, M., Bentivoglio, G. & Schottenberger, H. (2009). Ionic liquids as superiorsolvents for headspace gas chromatography of residual solvents with very lowvapor pressure, relevant for pharmaceutical final dosage forms. Journal of Chromatography A, 1216, 6020–6023. http://dx.doi.org/10.1016/j.chroma.2009.06.036
- Mulligan, K., J. & Mc., Cauley, H. (1995). Factors that influence the determination of residualsolvents in pharmaceuticals by automated static headspace sampling coupled to capillary GC–MS. Journal of Chromatographic Science, 33, 49–54. http://dx.doi.org/10.1093/chromsci/33.1.49
- Otero, R., Carrera, G., Dulsat, J.F., Fabregas, J.L. & Claramunt, J. (2004). Static headspace gaschromatogrphic method for quantitative determination of residual solventsin pharmaceutical drug substances according to European Pharmacopoeiarequirements.Journal of Chromatography A, 1057, 193–201. http://dx.doi.org/10.1016/j.chroma.2004.09.023
- Puranik, S.B., Varun, R.P., Lalitha, N, Pai, P. N. S. & Rao, G.K. (2008). Gas Chromatographic Determination of Methanol and Isopropyl Alcohol Impurities in Herbal Extracts; Pharmacological Reviews, 6 (32), 121-123.
- Pandey, S., Pandey, P., Kumar, R. & Singh, N.P. (2011). Residual solvent determination by head space gas chromatography with flame ionization detector in omeprazole API. Brazilian Journal of Pharmaceutical Sciences, 47, 379-384. http://dx.doi.org/10.1590/S1984-82502011000200019
- Qin, L., Hu, C. Q. & Yin, L.H. (2004). Establishment of a knowledge base for prescreening residual solvents in pharmaceuticals; Chromatographia, 59, 475–480.
- Residual Solvents <467>: The United States Pharmacopoeia, 30th ed., The United States Pharmacopeial Convention, Rockville, MD, 2007.
- Witschi, C. & Doelker, E. (1997). Residual solvents in pharmaceutical products: acceptable limits, influences on physicochemical properties, analytical methods and documented values; European Journal of Pharmaceutics and Biopharmaceutics, 43, 215–242. http://dx.doi.org/10.1016/S0939-6411(96)00037-9
- Yarramraju, S., Akurathai, V., Wolfs, K., Van Schepdael, A., Hoogmartens, J. & Adams, E. (2007). Investigation of sorbic acid volatile degradation products in pharmaceuticalformulations using static headspace gas chromatography; Journal of Pharmaceutical and Biomedical Analysis, 44, 456–463. http://dx.doi.org/10.1016/j.jpba.2007.01.020
How to Cite
Prafull Mathur, Suvigya Mathur, Anand Kumar Mishra, Tanaji Kunjir. Development and Validation of Static HS-GC Method for the Determination and Quantification of Residual Solvents of Bromhexine Hydrochloride (BHX).
J. Pharm. Technol. Res. Manag.. 2013, 01, 217-228
