CAPILLARY GAS-CHROMATOGRAPHIC ASSAY OF RESIDUAL METHENAMINE HIPPURATEIN EQUIPMENT CLEANING VALIDATION SWABS

A capillary gas chromatographic method is described for the determinat ion of methenamine hippurate residue in swabs collected from manufactu ring equipment surfaces. Any residual methenamine hippurate remaining on process equipment after cleaning is removed by swabbing with one we t polyester Absorbond(TM) swab (4 '' x 4 '') pre-moistened with water followed by a dry Absorbond swab. The residual methenamine hippurate i s chromatographed on a 30 x 0.32 mm (i.d.) Supelcowax(R)-10 capillary column of 0.25-micron film thickness. The amount of residual methenami ne hippurate is determined by comparing the ratio of methenamine hippu rate peak area response to that of p-cresol (internal standard) obtain ed for the sample to a linear calibration curve obtained for a series of standard solutions. The method is demonstrated to be sufficiently l inear, accurate, precise, sensitive and rugged for the determination o f low levels of methenamine hippurate on equipment surfaces. Using thi s method, the mean recovery of methenamine hippurate from spiked Absor bond swab samples contained in high density polyethylene bottles was 1 05.2%, with a relative standard deviation (RSD) of +/- 7.1% (n = 25). The mean recoveries of methenamine hippurate from spiked test plates f or '180 Grit' Stainless Steel, Teflon and WARCO White (neoprene and PV C) gasket material were 77.2, 96.1 and 50.6%, with RSDs of +/- 9.4 (n = 25), +/- 4.3 (n = 25) and +/- 36% (n = 20), respectively. Recovery c orrection factors have been incorporated into the method. The method w as successfully applied to the assay of actual equipment cleaning vali dation swab samples. Stability studies demonstrate that methenamine hi ppurate is not very stable on the equipment surfaces or in the swabs. It is recommended that the surfaces be swabbed immediately after clean ing and the swabs analyzed within 24 h after sample collection. The re sults demonstrate that in order to fully validate the cleaning procedu res, it is not only necessary to investigate the recovery of the drug from equipment surfaces and swabs but also that the stability of the d rug on the surfaces and swabs be determined. (C) 1998 Elsevier Science B.V. All rights reserved.