Quantitative analysis of preservatives drug preparations by microbiological assay

The stability of a preservative selected for incorporation into a drug preparation can only be determined by suitable tests applied at regular intervals, preferably over long periods. Chemical tests are available for a number of preservatives and some of them appear to be adequate but difficulties have occurred from time to time and studies were undertaken to develop microbiological tests. Chemical methods are usually more precise than biological assays but do not always measure the antimicrobial activity of the preservative as accurately. It is always possible that a preservative may break down, losing some of its effectiveness even though the chemical determinant upon which the test is based remains intact.Two assay methods were studied. One, a plate-diffusion procedure, was found suitable for assaying formol and preservatives containing mercury. Preservatives such as phenol, benzethonium chloride and others do not diffuse in an agar plate and a tube-plate bacterial count procedure was developed for this group. Procedures for both tests are described and some examples given.