QUANTITATIVE DETERMINATION OF RESIDUAL SOLVENTS IN PALONOSETRON API BY HS-GC METHOD
DOI:
https://doi.org/10.22159/ajpcr.2022.v15i2.43669Keywords:
Palonosetron, Residual solvents, Headspace gas chromatography, International conference on harmonizationAbstract
Objectives: Palonosetron is an antidote to 5-HT3 in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). The presence of residual solvents in pharmaceutical drug substances or products, as well as excipients, can have a detrimental effect on the product’s quality and stability. These substances must be evaluated for safety and efficacy. The primary purpose of this work is to establish a method for validating and quantifying residual solvents in palonosetron API using Head Space Gas Chromatography (HS-GC).
Methods: In the proposed HS-GC technique for the quantifying residual solvents - ethanol, acetone, methanol, acetonitrile, and isopropyl alcohol (IPA) in Palonosetron API, the headspace equilibrium was achieved at 100°C and analyzed by DB-624 column (30 m × 0.24 mm, 1.8 μm) with injector and detector temperature set at 200°C and 230°C respectively. The dissolving solvent was dimethyl sulfoxide (DMSO). After the initial holding time of 5mins, the temperature was increased to 120°C from 40°C in 20mins at a rate of 10°C/min using a flow rate of 10 ml/min and a split ratio of 1:25 with nitrogen as carrier gas. The approach created has been validated and quantified as per International Conference on Harmonization’s (ICH) guidelines.
Results: All the results obtained were within the ICH specified limits. The validation results for repeatability studies (%RSD values) were found to be <10; recovery studies values were in the range of 90–110% and for the selected linearity range 25–150 μg/ml the correlation coefficients(γ2) for all the solvents were observed to be >0.99.
Conclusion: A sensitive, simple, precise, and economic HS-GC method with Flame Ionization Detector (FID) was developed and validated to quantitatively determine the residual solvents in Palonosetron API.
Downloads
References
Aapro MS. Palonosetron as an antiemetic and anti-nausea agent in oncology. Ther Clin Risk Manag 2007;3:1009-20.
Hesketh P, Rossi G, Rizzi G, Palmas M, Alyasova A, Bondarenko I, Lisyanskaya A, et al. Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: A randomized dose-ranging pivotal study. Ann Oncol 2014;25:1340-6.
Grodowska K, Parczewski A. Analytical methods for residual solvents determination in pharmaceutical products. Acta Pol Pharm 2010;67:13- 26.
Bauer M, Barthelemy C. Handbook of Solvents. Vol. 1. Canada: ChemTec Publishing; 2001. p. 1129.
Hymer C. Residual solvent testing: A review of gas-chromatographic and alternative techniques. Pharm Res 2003;20:337-44.
Anerao A, Patil B, Pradhan N. Determination of residual dimethyl sulfate in methoxsalen drug substance by pre-column derivatization with static headspace gas chromatography. Int J Pharm Pharm Sci 2018;10:84-9.
Wenzyl T, Lankmayr EP. Comparative studies of static and dynamic headspace extraction of saturated short chain aldehydes from cellulose-based packaging materials. Anal Bioanal Chem 2002;372:649-53.
Nazarenko AY. Liquid phase headspace microextraction into a single drop. Am Lab 2004;36:30-5.
Westmorland DG, Rhodes GR. Analytical techniques for trace organic compounds-II. Detectors for gas chromatography. Pure Appl Chem 1989;61:1147-60.
Ravi JR, Reddy MP, Satya BR, Chowdary NV. An Improved Process for the Preparation of Pure Palonosetron Hydrochloride, WIPO (PCT), WO2009/010987A1; 2009.
Sigma-Aldrich Supelco: GC Column Selection Guide-Achieve Optimal Method Performance, US No. 800-325-3010; 2013. p. 1-6.
McNair H, Miller J. Basic Gas Chromatography. Vol. 471. New York, United States: Wiley; 1997. p. 17261-8.
Grant D. Capillary Gas Chromatography. Vol. 471. New York, United States: Wiley; 1996. p. 95371-6.
Rood D. A Practical Guide to the Care, Maintenance, and Troubleshooting of Capillary Gas Chromatographic Systems. Vol. 3. Missouri, United States: Huttig; 1991. p. 1898-904.
Lab-Training: Sample Injection Practices in Gas Chromatography; 2015.
Hage DS. Chromatography: Principles and Applications of Clinical Mass Spectrometry. Vol. 1. Amsterdam, Netherlands: Elsevier; 2018. p. 1-32.
International Conference on Harmonization, Impurities: Guidelines for Residual SOLVENTS. ICH Harmonized Tripartite Guideline; 1997.
Panigrahy UP, Reddy AS. 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.
Kumar GV, Sravanthi B, Aparna NG. Development and validation of RP-HPLC method for simultaneous estimation of netupitant and palonosetron in pharmaceutical dosage form. Indo Am J Pharm Sci 2018;5:16746-55.
Singh NP, Goud, VM, Sharma JV, Sirisha P, Devi C. A review on analytical methods for the determination of palonosetron in pharmaceutical formulation. Int J Pharm Sci Rev Res 2020;60:91-3.
Nalini CN, Ramachandran S, Uma G, Suresh P. Gas chromatography method development and method validation of residual solvent (isopropyl alcohol) in magnesium valproate. Int J Pharm Pharm Sci 2012;4:627-31.
Published
How to Cite
Issue
Section
Copyright (c) 2021 SUNNY GRACE GODE
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
