Validation of a high-performance thin-layer chromatographic method for trace analysis for some generic drugs affecting gastrointestinal function.

Abstract

To prevent cross-contamination between pharmaceutical products manufactured with the same equipment, cleanup procedures must be introduced before the manufacture of a new product begins. From an analytical point of view, it is crucial to select and validate a suitable analytical method to determine contaminants in the rinse water, swabs, and the placebo of the next product. High performance thin-layer chromatography (HPTLC) was chosen in our laboratory for this purpose and was optimized to meet the requirements of trace determination. The method was validated in terms of the limit of detection, limit of quantitation (LOQ), linearity close to the LOQ, sample preparation from the swab media and from the placebo of the next product made with the same equipment (recovery), precision, selectivity (interference from the swab and placebo matrixes), resolution (from related compounds), and robustness. The HPTLC method was applied to 2 different generic drugs affecting gastrointestinal function--the water-soluble H2-receptor antagonist ranitidine hydrochloride (RHCl) and the water-insoluble choleretic drug ursodeoxycholic acid (UDCA). Chromatography was performed on silica plates by using toluene-methanol-diethylamine (9 + 1 + 1, v/v/v) and n-heptane-ethyl acetate-glacial acetic acid (5 + 5 + 1, v/v/v) as the mobile phases for RHCl and UDCA, respectively. RHCl was measured in situ at 320 nm, whereas the detection of UDCA was performed at 502 nm after postchromatographic derivatization. The method was used for the determination of RHCl and UDCA in the swabs, the final rinse water, and the placebo batch after the cleanup process.