Development and validation of analytical methodology for near-infrared conformance testing of pharmaceutical intermediates.

An approach was developed to create and validate analytical methods to perform near-infrared (NIR) conformance testing on two isolated intermediates used in the manufacture of loracarbef monohydrate bulk drug substance. Method calibration sets were developed from second-derivative NIR reflectance spectra for 30 representative batches of each intermediate. In conformance testing, second-derivative NIR spectra for samples from newly manufactured batches are compared with the calibration set. If the new spectrum is not statistically different to the average of the calibration set, the sample passes the conformance test. Using authentic batch samples of typical and low-potency lots, the methods were validated for accuracy, selectivity, ruggedness and repeatability of the methods.