ESTIMATION OF RESIDUAL SOLVENTS IN NETUPITANT API BY HEADSPACE GAS CHROMATOGRAPHY
Keywords:Netupitant, Residual Solvents, HeadSpace Gas Chromatography, International Conference on Harmonization.
Objective: Residual solvents are undesirable components present in Active Pharmaceutical Ingredients (API), excipients, or drug products. To meet the specific quality-based requirements, the presence of these solvents in pharmaceutical products should be monitored to ensure their safety. The main objective of this work is to develop a new method for the determination of residual solvents in netupitant API by an HS-GC method with an FID detector.
Methods: An automated headspace GC method has been developed and validated for the estimation of the residual solvents- N-methyl pyrrolidine, xylene, toluene, and N, N Dimethylacetamide in netupitant API. The samples were dissolved in dimethyl sulfoxide and
the equilibrium headspace gas was formed at 80℃ which was analyzed using a DB-624
column (30m*0.53mm, 3.00µm) with injector and detector temperature set at 160℃ and 230℃ respectively. The initial oven temperature was set at 60℃ for 5mins and programmed at a rate of 10℃/min to the final temperature of 150℃, with a hold time of 5mins by maintaining the flow rate of 4.0ml/min with a split ratio of 1:10, and total run time of 20mins. Nitrogen was used as carrier gas. The method developed was validated as per International Conference for Harmonization (ICH) guidelines for repeatability, linearity, range, ruggedness, detection limit, quantification limit, and recovery studies.
Results: The linearity range selected was 50-350µg/ml and the correlation coefficient(γ2) values for all the solvents were found to be >0.99; recovery studies values were in a range of 90-110% and %RSD values were also found to be not more than 10 for the solvents.
Conclusion: A novel, accurate, sensitive, and simple method was described for estimating residual solvents in Netupitant API by Headspace Gas Chromatography (HS-GC) coupled with a Flame Ionization Detector (FID). Excellent results have been observed for all the validated parameters with good peak resolution and lesser retention times.
Prashant K. Singh, Lokesh K. Singh, Milind Pande, Ram B. Tripathi, Steps to be considered during method development and validation for analysis of residual solvents by Gas Chromatography. Int Res J Pharm App Sci 2013, 3: 74-80.
Katarzyna Grotowski and Andrzej Barczewski, iAnalytical methods for Residual Solvents determination in Pharmaceutical Products. Acta Poloniae Pharmaceutica – Drug Research 2010, 67:13-26.
Colin D Medley, Jacob Kay, Yi Li, Jason Gruen Hagen, Peter Yehl, Nik P Chetwyn, Quantification of residual solvents in antibody-drug conjugates using gas chromatography. Analytica Chimica Acta 2014,850: 92-6.
Shoeb Al Ahmad, Mohd. Amer Almardini, Mahzia Yahia, Validated HS-GC-FID method for determination of residual ethanol in a solid dosage form. Res J Pharm Tech 2014,7: 184-7.
A. Naddaf and J. Balla, Comparison of quantitative analytical methods in HS GC of residual solvents. Springer, 2000, S241-8.
Chandrakant Sojitra, Ajay Tehare, Chintan Dholakla, Padmaja Sudhakar, Sameer Agarwal, Kumar K. Singh, Development and validation of residual solvent determination by headspace gas chromatography in Imatinib Mesylate API. SN Applied Sciences 2019, 1:233-9
Siva Sai Kiran B, Y Nayudamma Chowdary, Sree Lakshmi V., S.K. Shrivastava, Pugazhendhi S., Development and validation of Head pace Gas Chromatographic Method for determination of Residual Solvents in Bosentan Monohydrate. Int J PharmTech Res 2014, 2:421-7.
Dr. Anthony Melvin Crasto, New Drug Approvals: Fosnetupitant, EU 2015.
Uttam Prasad Panigrahy, A. Sunil Kumar Reddy, A novel validated RP-HPLC-DAD method for simultaneous estimation of Netupitant and Palonosetron in bulk and pharmaceutical dosage form with forced degradation studies. Int J ChemTech Res. 2015, 8: 317-37.
Structure of Netupitant: Adooq Biosciences. www.biogenuix.com.
Kishore J., P Rao K, Development and validation of a gas chromatography headspace method for the simultaneous quantification of six volatile impurities in sumatriptan succinate API and its pharmaceutical dosage forms. Asian J Pharma Clin Res 2020, 13: 210-8.
Mishra G., V. Saxena, S. Jawla, V.K. Srivastava, Method development and validation for the determination of residual solvents in omeprazole API by using Headspace Gas Chromatography. Asian J Pharma Clin Res 2013,7: 54-6.
Dr. Gampa Vijay Kumar, B. Sravanthi, N. Gayathri Aparna, Development and validation of RP-HPLC method for simultaneous estimation of netupitant and palonosetron in the pharmaceutical dosage form. Indo American J Pharma Sci 2018,5:16746-55.
Jahnavi N. & Saravanan V.S., Method Development and Validation for the determination of residual solvents in methocarbamol pure drug by HS-GC. I J Res Pharma Che 2012, 2: 456-67.
Rele R.V. & Mali R.N., Determination of Residual Solvents in Citalopram hypo bromide by Gas Chromatography. Am J PharmTech Res 2012, 2: 619-25.
Ramos C.S., Development and Validation of a headspace chromatographic method for determination of residual solvents in five drug substances. Int J Pharma Sci Invention 2013, 2: 36-41.
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