Abstract
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.
Highlights
Palonosetron, chemically known as (3aS)-2-[(3S)-Quinuclidin-3-yl]2,3,3a,4,5,6-hexahydro- 1H-benzo[de]-isoquinolin-1-one; is 5-HT3 receptor antagonist suggested for the treatment of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and post-operative nausea and vomiting
In the proposed Head Space Gas Chromatography (HS-Gas chromatography (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
All the results obtained were within the International Conference on Harmonization (ICH) specified limits
Summary
Palonosetron, chemically known as (3aS)-2-[(3S)-Quinuclidin-3-yl]2,3,3a,4,5,6-hexahydro- 1H-benzo[de]-isoquinolin-1-one; is 5-HT3 receptor antagonist suggested for the treatment of nausea and vomiting associated with moderately-emetogenic cancer chemotherapy and post-operative nausea and vomiting. Residual solvents (RS) are frequently used in the manufacture of pharmacological compounds, excipients, and finished pharmaceutical products. Pharmaceutical products must be tested for ‘RS when production or purification of processes known to produce or purify solvents’ according to ICH harmonized guidelines set up by the European Union, Japan, and the United States for the registration of pharmaceutical products [4]. These guidelines specify the analytical procedures used to identify and quantify residual solvents, as well as the permitted acceptable concentration limits.
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