DETERMINATION OF RESIDUAL DIMETHYL SULFATE IN METHOXSALEN DRUG SUBSTANCE BY PRE-COLUMN DERIVATIZATION WITH STATIC HEADSPACE GAS CHROMATOGRAPHY
DOI:
https://doi.org/10.22159/ijpps.2018v10i8.27670Keywords:
MethoMethoxsalen, Dimethyl sulfate, GC-HS, Derivatization, Validationxsalen, derivatization, validationAbstract
Objective: Dimethyl sulfate has been highlighted as potential genotoxic and carcinogenic impurity. A sensitive Headspace gas chromatography (HS-GC) method with pre-column derivatization was developed and validated for the determination of dimethyl sulfate impurity in methoxsalen active pharmaceutical ingredient.
Methods: HS-GC method on the column Agilent DB-5, 30m X 0.53 mm, film thickness 1.5 µm, with flame ionization detector (FID) was used. Derivatization reagent concentration, time of reaction and pH of the solution were optimized during method development. This analytical method was evaluated by performing method validation as per ICH guideline.
Results: The proposed method was specific, linear, accurate, rugged and precise. The calibration curves showed good linearity over the concentration range of 0.5 μg/ml to 3.0 μg/ml and the correlation coefficient was 0.999. Method had very low limit of detection (LOD) and limit of quantification (LOQ) 2.0 μg/g and 5.0 μg/g respectively. Accuracy was observed within 98.1%–104.5%.
Conclusion: The developed method was demonstrated to be accurate, robust and sensitive for the determination of dimethyl sulfate impurity in methoxsalen drug substance.
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