INVESTIGATION OF MUSTY ODOR IN PHARMACEUTICAL PRODUCTS BY DYNAMIC HEADSPACE GAS-CHROMATOGRAPHY

A musty odour detected in several solid oral pharmaceutical products is attributed to the presence of chloroanisoles, principally 2,4,6-trichloroanisole and secondarily 2,3,4,6-tetrachloroanisole. The chloroanisoles are believed to have been formed in cardboard shippers via microbial methylation of chlorophenol precursors. The source of the chlorophenols in the shippers is not certain, but evidence suggests bleaching of pulp to be a probable source. A microbiological survey of typical product storage facilities revealed the presence of six genera of fungi that are known to be capable of methylating chlorophenols. The musty-smelling chloroanisoles contaminated the product by permeating the high-density polyethylene product bottles. No microbial contamination was found in any unopened product bottle. The principal technique utilized was dynamic headspace gas chromatography with flame-ionization, photoionization, electrolytic conductivity (halogen-model) and parallel chromatographic sniffing as detection modes. The musty odour contamination was eliminated by implementing several corrective actions in the storage facility.