Developing multiple high-throughput GLP methods for an investigational drug candidate in various matrices within a...

In early pharmaceutical product development, an investigational drug candidate is typically dosed to various species for toxicological and pharmacokinetic studies. Most of these studies require multiple analytical methods that have to be validated with good laboratory practice (GLP) prior to the application in regulated studies. Usually, these analytical methods are developed in either a serial or parallel approach. For either approach, the development of multiple analytical methods takes tremendous work from scientists and instruments, and thus is not cost-effective. In this respect, a new strategy has been developed for simultaneous GLP method development using liquid chromatographic separation and tandem mass spectrometric detection. This high-throughput approach allows system suitability, carryover, calibration curve, accuracy, precision, matrix effect and selectivity to be evaluated in one 96-well plate. The strategy has been successfully implemented for multiple investigational drug candidates at Abbott Laboratories. The methods developed with this strategy are accurate, precise, selective, robust and matrix-independent. As an example, ABT-279 was used to demonstrate the feasibility of this strategy.