LC-MS/MS assay for N1 -methylnicotinamide in humans, an endogenous probe for renal transporters

Bioanalysis
Lina LuoRagu Ramanathan

Abstract

N1-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. A hydrophilic interaction liquid chromatography-MS/MS assay, to quantify 1-NMN, in human plasma and urine is reported. 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. 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.

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Methods Mentioned

BETA
ion-exchange chromatography

Software Mentioned

PeakView
GraphPad
Prism
Chemspider
MultiQuant

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