LC–MS/MS assay for N1-methylnicotinamide in humans, an endogenous probe for renal transporters. (11th May 2018)

• Record Type: Journal Article
• Authors: Luo, Lina; Kay, Jared; Zhang, Jenny; Holliman, Christopher L; Rodrigues, A David; Dowty, Martin; Banfield, Christopher; Ramanathan, Ragu
• Is Part Of: Bioanalysis. Volume 10:Number 9(2018)
• Page Start: 673
• Page End: 689
• Publication Date: 2018-05-11
• Subjects: drug–drug interactions -- endogenous biomarkers -- HILIC–MS/MS -- N1-methylnicotinamide -- renal transporters; Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio-2017-0272
• Languages: English
• ISSNs: 1757-6180

Abstract

Background: N 1 -methylnicotinamide (1-NMN) has been proposed as a potential clinical biomarker to assess drug–drug interactions involving organic cation transporters (OCT2) and multidrug and toxin extrusion protein transporters.Results: A hydrophilic interaction liquid chromatography–MS/MS assay, to quantify 1-NMN, in human plasma and urine is reported.Materials & methods: A hydrophilic interaction chromatography (HILIC)-tandem mass spectrometry (MS/MS) assay to quantify 1-NMN in human plasma and urine is reported. The basal 1-NMN levels in plasma and urine were 4–120 and 2000–15, 000 ng/ml, respectively.Conclusion: 1-NMN plasma AUCs increased two- to fourfold versus placebo following the administration of a clinical candidate that in vitro experiments indicated was an OCT2 inhibitor. The described hydrophilic interaction liquid chromatography–MS/MS assay can be used to assess a clinical compound candidate for the inhibition of OCT2 and multidrug and toxin extrusion protein transporter in first-in-human studies.