Rapid, Sensitive, General Purpose Cleaning Verification HPLC Methods Using Fused-Core Particle (FCP) Columns On Conventional Instrumentation

Verification of the removal of the drug residue from multi-product manufacturing equipment is required by GMP regulations and suitability of applied analytical methods is judged with a combination of sesitivity and selectivity - and because the release of the equipment is dependent speed. The FDA does not set a quantitative acceptance specifications, but the commonly used limit is based on not more than 0.1% of a dose carried over into single dose of the next product. Translation of this into an analytical limit combines the total product contact area, the mass (or volume) of product containing the surface, the mass (or volume) of each dose unit, the sampled area, and the fraction of verification sample used for analysis. The requisite limits are commonly measured in ng/mL. The ubiquity of HPLC in drug analysis makes it an attractive choice for cleaning validation. Methods qualified for cleaning validation are often adaptations of drug substance methods. These methods are capable of determining the drug and its related impurities, but the ability to simultaneously measure multiple closely related analytes comes at the expense of run time and is not needed in cleaning validation.

Resulation, limits of detection and quantitation and run time in HPLC analyses are improved by reducing the width of eluted bands. Contributions to bandwidth include both column(practicle size,packing structure and resistence to mass transfer in the stationary and mobile phases) and extracolumn volumes (injection, unswept and tubing). Columns packed with 5um fully porous particles have been the standard for conventional HPLC for twenty-five years. Smaller particle packings (3-um) have been available almost as long and offer higher efficiency (lower band dispersion) on conventional instrumentation, but require higher pumping pressures due to lower bed permeability.