A Strategy to Determine Leachables in Liquid Drug Products

A strategy has been developed to expand the analytical capability of HPLC methods which initially were designed to only monitor drug product stability, but now are designed to detect and quantify both drug substance impurities and leachable compounds. This strategy for expanding the analytical capability of HPLC methods is based upon two factors, the use of a dual detection system and an assessment of the chromatographic resolution capability. Chromatographic resolution is determined by using a series of reference compounds, which have distinct partition properties, to calibrate the analytical range of the method. Additionally the data generated to calibrate the resolution range can also provide a statistical assessment as to the probability that a set number of peaks can be baseline resolved over the specified range. Examples will be presented in this manuscript of how this strategy has been applied in the design of an HPLC method to detect both drug substance and process impurities (e.g. leachables). Additional examples will be presented demonstrating the effectiveness these HPLC methods can have in identifying unknown leachables that are the product of drug product exposed to polymeric material (e.g. Viton rubber “O” rings, elastomeric stoppers, etc.) that are commonly used in the manufacturing and packaging pharmaceuticals.