Head To Head Linearity Comparison Of An LC/MS/MS Assay

By A. Witkowski , C. Serpe , G. Baker , D. Gray, J. Burrows, K. Watson , and J. Chiu

To perform a head to head linearity comparison of the Finnigan TSQ 7000 and the Sciex API 3000 LC/MS/MS systems.

An LC/MS/MS assay based on solid phase extraction was developed for a proprietary new chemical entity and its metabolite in human plasma. Initially, the assay was validated on the Finnigan TSQ 7000. The assay linearity on the Finnigan was assessed by analyzing 6 replicates of each calibration standard over the validated range, as well as above and below these concentrations. To compare the linearity of the Sciex, the API 3000 was tuned for both analytes and 6 replicates of each calibration standard were run. Both data sets were evaluated by constructing sensitivity plots (response/concentration versus log concentration) and comparing the observed behavior to theoretical models. In addition, the mean percent biases using various regression fits were calculated. The background signal as a function of concentration injected was also examined.

Both LC/MS/MS platforms performed well, and conditions were found that gave less than ~10% average bias on both instruments. Based on the sensitivity plots and their theoretical fits, the Sciex API 3000 is more linear over the validated concentration range. Furthermore, the Sciex showed smaller mean percent bias values than the Finnigan. The Sciex also had lower background signals after high concentrations of drug were injected.