Capillary gas chromatographic assay of residual methenamine hippurate in equipment cleaning validation swabs.
A capillary gas chromatographic method is described for the determination of methenamine hippurate residue in swabs collected from manufacturing equipment surfaces. Any residual methenamine hippurate remaining on process equipment after cleaning is removed by swabbing with one wet polyester Absorbond swab (4" x 4") pre-moistened with water followed by a dry Absorbond swab. The residual methenamine hippurate is chromatographed on a 30 x 0.32 mm (i.d.) Supelcowax-10 capillary column of 0.25-micron film thickness. The amount of residual methenamine hippurate is determined by comparing the ratio of methenamine hippurate peak area response to that of p-cresol (internal standard) obtained for the sample to a linear calibration curve obtained for a series of standard solutions. The method is demonstrated to be sufficiently linear, accurate, precise, sensitive and rugged for the determination of low levels of methenamine hippurate on equipment surfaces. Using this method, the mean recovery of methenamine hippurate from spiked Absorbond swab samples contained in high density polyethylene bottles was 105.2%, with a relative standard deviation (RSD) of +/- 7.1% (n = 25). The mean recoveries of methenamine hippurate from spiked test plates for '180 Grit' Stainless Steel, Teflon and WARCO White (neoprene and PVC) 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 correction factors have been incorporated into the method. The method was successfully applied to the assay of actual equipment cleaning validation swab samples. Stability studies demonstrate that methenamine hippurate is not very stable on the equipment surfaces or in the swabs. It is recommended that the surfaces be swabbed immediately after cleaning and the swabs analyzed within 24 h after sample collection. The results demonstrate that in order to fully validate the cleaning procedures, it is not only necessary to investigate the recovery of the drug from equipment surfaces and swabs but also that the stability of the drug on the surfaces and swabs be determined.
Mirza
T
T
Department of Quality Control, Hoechst Marion Roussel, Cincinnati, OH 45215, USA.
George
R C
RC
Bodenmiller
J R
JR
Belanich
S A
SA
D000892:Anti-Infective Agents, Urinary / Q000032:analysis*; D002138:Calibration; D002849:Chromatography, Gas; D004339:Drug Compounding / Q000295:instrumentation*; D004350:Drug Residues / Q000032:analysis*; D004355:Drug Stability; D006626:Hippurates / Q000032:analysis*; D008709:Methenamine / Q000031:analogs & derivatives* / Q000032:analysis; D009387:Neoprene / Q000032:analysis; D011138:Polytetrafluoroethylene / Q000032:analysis; D012015:Reference Standards; D015203:Reproducibility of Results; D013193:Stainless Steel / Q000032:analysis
D000892:Anti-Infective Agents, Urinary; D006626:Hippurates; D013193:Stainless Steel; D011138:Polytetrafluoroethylene; D009387:Neoprene; D008709:Methenamine; C011481:methenamine hippurate