Determination of residual solvent levels in bulk pharmaceuticals by capillary gas chromatography

Abstract

A method is described by use of which the levels of residual solvents in bulk pharmaceutical materials can be determined quantitatively by gas chromatography using a wide-bore wall-coated open tubular column. The method has been found to be suitable for a wide range of solvents and sample matrices and is widely used in this laboratory. Quantification is achieved by using methylcyclohexane as internal standard. The pharmaceutical material is either dissolved in a suitable solvent or the solvent residues are extracted from insoluble matrices. Linearity of response for a number of solvents was demonstrated. The retention times of the solvents, relative to the internal standard, and their limits of detection are presented. The reproducibility of response and retention time of the solvents was also determined. Recognized limitations are discussed.