A Multiplatform Approach for the Discovery of Novel Drug-Induced Kidney Injury Biomarkers.

Drug-induced kidney injury (DIKI) is a common toxicity observed in pharmaceutical development. We demonstrated the use of label-free liquid chromatography-mass spectrometry (LC-MS) and multiplex liquid chromatography-single reaction monitoring (LC-SRM) as practical extensions of standard immunoassay based safety biomarker assessments for identification of new toxicity marker candidates and for improved mechanistic understanding. Two different anticancer drugs, doxorubicin (DOX) and cisplatin (cis-diamminedichloridoplatinum, CDDP), were chosen as the toxicants due to their different modes of nephrotoxicity.

Quantitative determination of residual active pharmaceutical ingredients and intermediates on equipment surfaces by ion mobility spectrometry.

Ion mobility spectrometry (IMS) is an analytical technique that separates ions based on their gas phase mobility at atmospheric pressure. Since gas phase ion mobility is a function of the shape and structure of the ion, this technique has the potential to provide unique specificity and selectivity. Furthermore, IMS is very sensitive (subnanogram detection limits for many small molecules), and a single analysis is typically completed within 1 min.

Sphingosine kinase 1 is a negative regulator of CD4+ Th1 cells.

CD4+ Th1 cells produce IFN-gamma, TNF-alpha, and IL-2. These Th1 cytokines play critical roles in both protective immunity and inflammatory responses. In this study we report that sphingosine kinase 1 (SPHK1), but not SPHK2, is highly expressed in DO11.