Quantification of Niacin and Its Metabolite Nicotinuric Acid in Human Plasma by LC-MSMS: Application to a Clinical Trial of a Fixed Dose Combination Tablet of Niacin Extended-ReleaseSimvastatin (500 mg10 mg)‎ in Healthy Chinese Volunteers

Abstract EN

Our paper aimed to develop rapid, sensitive, and specific LC-MS/MS method for the quantification of niacin (NA) and its metabolite nicotinuric acid (NUA) in human plasma.

Following protein precipitation with acetonitrile, the NA, NUA, and internal standard (5-fluorouracil) were separated on a Zorbax 300SB-C8 column (250 mm × 4.6 mm, 5 μm) with a mobile phase consisting of methanol-2 mM ammonium acetate (3 : 97, v/v) at a flow rate of 1 mL/min (split 1 : 1).

A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in negative ion mode.

The linear concentration ranges of the calibration curves were 5–800 ng/mL for NA and NUA.

The intra-assay RSD for quality control (QC) samples were from 5.0% to 8.7% for NA, and 5.5% to 7.6% for NUA.

The interassay RSD for QC samples were from 2.8% to 9.4% for NA, and 3.7% to 5.8% for NUA.

The relative errors for QC samples were from −2.2% to 2.3% for NA, and −0.6% to 3.2% for NUA.

The method was successfully applied to the investigation of the pharmacokinetic profiles of NA, NUA in human after single dose administration of Niacin extended-release/Simvastatin tablet (500 mg/10 mg).