DETERMINATION OF RESIDUAL SOLVENTS IN PAROXETINE BY HEADSPACE GAS CHROMATOGRAPHY
Keywords:Paroxetine, Gas chromatography, Flame ionization detector
Objectives: A simple and sensitive gas chromatographic method was developed and validated for simultaneous determination of acetone and isopropyl alcohol in paroxetine.
Methods: The separation was achieved on ZB-1, 30 m length × 0.53 mm ID, and film thickness 5 μm using a flame ionization detector (FID) with gradient column oven temperature program. The injection was carried out in split mode, with a split ratio of 10:1. Dimethylacetamide was selected as a diluent to obtain good sensitivity along with the recovery. 1-propanol was used as an internal standard which employed for area ratio method.
Results: The developed gas chromatographic method offers symmetric peak shape, good resolution of 2.3 min, and reasonable retention time for the solvents acetone 9.210 min and isopropyl alcohol 9.845 min. The limit of detection for acetone and isopropyl alcohol was 26.72 μg/ml and 82.96 μg/ml, respectively. Limit of quantitation for acetone and isopropyl alcohol was 80.96 μg/ml and 251.39 μg/ml, respectively. Precision was 0.83 and 0.63. Linearity was y = 0.0004x, R2 = 0.9988 for acetone, and y = 0.0001x+0.0021, R2 = 0.9987 for isopropyl alcohol, and accuracy along with robustness is performed and acceptable results were obtained.
Conclusion: The proposed, developed method was demonstrated to be simple, sensitive, linearity, accurate, and robust, hence can be used to determine the residual organic solvents in paroxetine drug substance and drug product.
U.S. Food and Drug Administration. Q3A Impurities in New Drug Substances. Washington, DC: Food and Drug Administration; 2003.
U.S. Food and Drug Administration. Q3B Impurities in New Drug Products. United States: Food and Drug Administration; 2006.
Gorog S. Identification and Determination of Impurities in Drugs. Amsterdam: Elsevier Science, B.V; 2000.
Bhowmik H, Venkatesh DN. Nanosponges: A review. Int J Appl Pharms 2018;10:1-5.
Hovorka S, Schöneich C. Oxidative degradation of pharmaceuticals: Theory, mechanisms and inhibition. J Pharm Sci 2001;90:253-69.
Roy J. Pharmaceutical impurities – a mini-review. AAPS PharmSciTech 2002;3:E6.
ICH Harmonised Tripartite Guidelines: Q3A(R). Impurities in New Drug Substances International Conference on Harmonisation; 2003.
ICH Harmonisation for Better Health. Q3B(R). Impurities in New Drug Products Guidelines; 2003.
ICH Guideline. Impurities: Guideline for Residual Solvents; 1997.
International Conference on Harmonisation. Stability Testing of New Drug Substances and Products Q1A(R2); 2003.
Haky JE, Stickney TM. Automated gas chromatographic method for the determination of residual solvents in bulk pharmaceuticals. J Chromatogr 1985;321:137-44.
Markovich RJ, Ong S, Rosen J. J Chromatogr Sci 1997;35:584-92.
Zhu JY, Chai XS. Some recent developments in headspace gas chromatography. Curr Anal Chem 2005;1:79-83.
Nouws HP, Delerue-Matos C, Barros AA, Rodrigues JA. Electroanalytical determinationof paroxetine in pharmaceuticals. J Pharm Biomed Anal 2006;42:341-6.
Erk N, Biryol I. Voltammetric and HPLC techniques for the determination of paroxetine hydrochloride. Pharmazie 2003;58:699 704.
Robert S, Genowefa M, Marcin K. Determination of fluoxetine and paroxetine in Planar pharmaceutical formulations by densitometric and videodensitometric TLC. J Chromatogr 2003;16:19-22.
Venkatachalam A, Chatterjee VS. Stability-indicating high-performance thin layer chromatography determination of paroxetine hydrochloride in bulk drug and pharmaceutical formulations. Anal Chim Acta 2007;598:312-7.
Zainaghi IA, Lanchote VL, Queiroz RH. Determination of paroxetine in geriatric depression by high-performance liquid chromatography. Pharmacol Res 2003;48:217-21.
Zhu Z, Neirinck L. High-performance liquid chromatography-mass spectrometry method for the determination of paroxetine in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2002;780:295 300.
Massaroti P, Cassiano NM, Duarte LF. Validation of a selective method for determination of paroxetine in human plasma by LC-MS/MS. J Pharm Pharm Sci 2005;8:340-7.
Jhee OH, Seo HK, Lee MH, Jeon YC, Shaw LM, Lee SH, et al. Determination of paroxetine in plasma by liquid chromatography coupled to tandem mass spectrometry for pharmacokinetic and bioequivalence studies. Arzneimittelforschung 2007;57:455-61.
British Pharmacopoeia 2003. London, UK: The Stationary Office; 2003.
United States Pharmacopeial Convention. The United States Pharmacopeia. The National Formulary 26. 31th ed. Rockville, MD, USA: United States Pharmacopeia; 2008.
Eap CB, Bouchoux G, Amey M, Cochard N, Savary L, Baumann P. Simultaneous determination of human plasma levels of citalopram, paroxetine, sertraline, and their metabolites by gas chromatography-
mass spectrometry. J Chromatogr Sci 1998;36:365-71.
Leis HJ, Windischhofer W, Fauler G. Improved sample preparation for the quantitative analysis of paroxetine in human plasma by stable isotope dilution negative ion chemical ionisation gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2002;779:353-57.
Lai CT, Gordon ES, Kennedy SH, Bateson AN, Coutts RT, Baker GB, et al. Determination of paroxetine levels in human plasma using gas chromatography with electron-capture detection. J Chromatogr B Biomed Sci Appl 2000;749:275-9.
Labat L, Deveaux M, Dallet P, Dubost JP. Separation of new antidepressants and their metabolites by micellar electrokinetic capillary chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2002;773:17-23.
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