Cleaning level acceptance criteria and a high pressure liquid chromatography procedure for the assay of Meclizine Hydrochloride residue in swabs collected from pharmaceutical manufacturing equipment surfaces.

A method using pharmacologically based and visual limit of detection criteria to determine the acceptable residue level for Meclizine Hydrochloride (MH) on pharmaceutical manufacturing equipment surfaces after cleaning is described. A formula was used in order to determine the pharmacologically safe cleaning level for MH. This level was termed as specific residual cleaning Level (SRCL) and calculated to be 50 microg 100 cm(-2). The visual limit of detection (VLOD) was determined by spiking different levels of MH on stainless steel plates and having the plates examined by a group of observers. The lowest level that could be visually detected by the majority of the observers, 62.5 microg 100 cm(-2), was considered as the VLOD for MH. The lower of the SRCL and VLOD values, i.e. 50 microg 100 cm(-2), was therefore chosen as the cleaning acceptance criterion. A sensitive reversed-phase HPLC method was developed and validated for the assay of MH in swabs used to test equipment surfaces. Using this method, the mean recoveries of MH from spiked swabs and '180-Grit' stainless steel plates were 87.0 and 89.5% with relative standard deviations (RSD) of +/- 3.3 and +/- 2.4%, respectively. The method was successfully applied to the assay of actual swab samples collected from the equipment surfaces. The stability of MH on stainless steel plates, on cleaning swabs and in the extraction solution was investigated.

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.