Abstract
A static headspace gas chromatographic (sHS-GC) method for quantitative determination of residual organic solvents in eprosartan mesylate drug substance is developed. SE-30 capillary column (30 m x 0.25 mm i.d., 0.5 μm film thickness) and FID detector are adopted. Response surface methodology (RSM) has been successfully applied to obtain the optimum headspace conditions: the equilibrium temperature is set at 80 °C, equilibrium time at 40 min and the ionic strength (K2CO3) at 4.0 mol/L. Injection is carried out in split mode, with a split ratio of 15. A 0.1 mol/L NaOH solution is proposed as the sample solvent to obtain good sensitivity and recovery. The method of internal standard is used for quantitative analysis of three solvents utilized in the synthesis of eprosartan mesylate: methanol, dichloromethane and pyridine. Validation is performed within the requirements of ICH validation guidelines Q2A and Q2B. System suitability requirements described in the Chinese Pharmacopoeia are checked. Limits of detection and quantitation, precision, linearity and accuracy are determined, and acceptable results are obtained. The proposed method is demonstrated to be simple, accurate and sensitive, and can be used to determine the residual organic solvents in eprosartan mesylate drug substance.
Keywords: Eprosartan mesylate, Gas chromatography, Internal standard, Response surface methodology, Residual solvents, Static Headspace, static headspace gas chromatographic (sHS-GC), FID detector, Response surface methodology (RSM), ICH validation guidelines Q2A and Q2B, Limits of detection, Limits of quantitation, Box, –, Behnken Design Matrix
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