LC-MS/MS assay for N 1 -methylnicotinamide in humans, an endogenous probe for renal transporters

LC-MS/MS assay for N 1 -methylnicotinamide in humans, an endogenous probe for renal transporters

N -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 h...

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Veröffentlicht in:Bioanalysis 2018-05, Vol.10 (9), p.673-689
Hauptverfasser: Luo, Lina, Kay, Jared, Zhang, Jenny, Holliman, Christopher L, Rodrigues, A David, Dowty, Martin, Banfield, Christopher, Ramanathan, Ragu
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container_end_page 689
container_issue 9
container_start_page 673
container_title Bioanalysis
container_volume 10
creator Luo, Lina
Kay, Jared
Zhang, Jenny
Holliman, Christopher L
Rodrigues, A David
Dowty, Martin
Banfield, Christopher
Ramanathan, Ragu
description N -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.
doi_str_mv 10.4155/bio-2017-0272
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title LC-MS/MS assay for N 1 -methylnicotinamide in humans, an endogenous probe for renal transporters
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