Validation of LC-MS/MS methods for quantitative analysis of kynurenine pathway metabolites in human plasma and cerebrospinal fluid.

Dysregulation of the kynurenine metabolic pathway has been reported in several neurological conditions. Sensitive and selective LC-MS/MS methods have been validated for six kynurenine pathway metabolites in human cerebrospinal fluid and plasma. For each matrix, we validated three methods - one for the simultaneous determination of kynurenine, kynurenic acid, anthranilic acid and 3-hydroxy-kynurenine (four-analyte assay), one for quinolinic acid and one for tryptophan - using stable-isotopically labeled internal standards.

Development and validation of bioanalytical methods to support investigations of AZD9496 in the clinic.

AZD9496 is an oral nonsteroidal, potent and selective antagonist and degrader of ER-α. Two major active metabolites (M3 and M5 as diastereomers) were identified in humans. Multianalyte, sensitive LC-MS/MS method in human plasma was developed and validated that overcame the challenges encountered.