Validated HPLC Method for the Determination of Residues of Acetaminophen, Caffeine, and Codeine Phosphate on Swabs Collected from Pharmaceutical Manufacturing Equipment in Support of Cleaning Validation†

Abstract

A high performance liquid chromatography (HPLC) method was developed for the simultaneous determination of residues of acetaminophen (paracetamol), caffeine, and codeine phosphate on swabs collected from pharmaceutical manufacturing equipment surfaces. Any residues of the compounds remaining on process equipment after cleaning are removed by swabbing with wet Texwipe® swabs, premoistened with methanol/water, followed by dry Texwipe® swabs. These residues are extracted from the swabs by means of an ultrasonic bath and the amounts of the compounds are determined. The chromatography was performed in the isocratic mode on a RP‐18 column using a mobile phase consisting of 25 mM ortho‐phosphoric acid and acetonitrile (90:10, v/v). UV‐ and fluorescence detection was performed in order to improve the method's sensitivity. The method was validated by specificity, linearity, limit of detection, and limit of quantification, accuracy, and precision for the residues of acetaminophen (paracetamol), caffeine, and codeine phosphate on equipment surfaces. Stability studies have demonstrated the stability of the residual active compounds on equipment surfaces and on the swabs. †Parts of this paper were presented at the 29th International Symposium on High Performance Liquid Phase Separations & Related Techniques, “HPLC 2005”, June 26–30, 2005, Stockholm, Sweden.