Abstract
A highly selective and sensitive liquid chromatographic tandem mass spectrometric (LC-MS–MS) method was developed and validated for the quantitation and pharmacokinetic study of niacin (NA) and its two metabolites niacinamide (NAM) and nicotinuric acid (NUR) in human plasma. Protein precipitation with 14% perchloric acid solution was selected for sample preparation, and ganciclovir was used as an internal standard. Separation was on a Phenomenex Curosil-PFP (250 mm × 4.6 mm, 5 μm) column by a multiple steep steps linear gradient elution with mobile phase consisting of water and methanol, both containing 0.1% formic acid, pumped at a flow rate of 1 mL min−1. The determination was optimized and carried out with positive electrospray ionization by selective multiple reaction monitoring. The method was linear in the concentration range of 15–2,000 ng mL−1 for NA, 70–2,000 ng mL−1 for NAM and 10–2,000 ng mL−1 for NUR, by standard addition calibration. The application of LC-MS–MS was demonstrated for the specific and quantitative analysis of NA, NAM and NUR in human plasma from a pharmacokinetic study in 12 healthy Chinese volunteers treated with three incremental doses of niacin extended-release/lovastatin tablets and an additional steady-state regime.
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Hageman GJ, Stierum RH (2001) Mutat Res 475:45–56. doi:10.1016/S0027-5107(01)00078-1
Pieper JA (2002) Am J Manag Care 8:S308–S314
Tavintharan S, Kashyap ML (2001) Curr Atheroscler Rep 3:74–82. doi:10.1007/s11883-001-0014-y
Mrochek JE, Jolley RL, Young DS, Turner WJ (1976) Clin Chem 22:1821–1827
Ding RW, Kolbe K, Merz B, Vries JD, Weber E, Benet ZB (1989) Clin Pharmacol Ther 46:642–647. doi:10.1038/clpt.1989.200
Iwaki M, Murakami E, Kakehi K (2000) J Chromatogr B 747:229–240. doi:10.1016/S0378-4347(99)00486-7
Murray MF (2003) Clin Infect Dis 36:453–460. doi:10.1086/367544
Jacobson EL, Giacomoni PU, Roberts MJ, Wondrak GT, Jacobson MK (2001) J Photochem Photobiol B 63:141–147. doi:10.1016/S1011-1344(01)00211-1
AOAC (2000), Methods 985.34, 944.13, 968.32 and 975.41. In: Horwitz W (ed) Offical methods of analysis, 17th edn, Association of Official Analytical Chemists International, Gaithersburg, MD
Rose-Sallin C, Blake CJ, Genoud D, Tagliaferri EG (2001) Food Chem 73:473–480. doi:10.1016/S0308-8146(01)00121-2
Becker B, Hummel K (1990) Arzneimittelforschung 40:573–575
Iwaki M, Murakami E, Kikuchi M, Wada A, Ogiso T, Oda Y, Kubo K, Kakehi K (1998) J Chromatogr B 716:335–342. doi:10.1016/S0378-4347(98)00327-2
Zarzycki PK, Kowalski P, Nowakowska J, Lamparczyk H (1995) J Chromatogr A 709:203–208. doi:10.1016/0021-9673(95)00247-K
Hengen N, Seiberth V, Hengen M (1978) Clin Chem 24:1740–1743
Takikawa K, Miyazaki K, Arita T (1982) J Chromatogr 233:343–348. doi:10.1016S0378-4347(00)81765-X
Tsuruta Y, Kohuhi K, Ishida S, Ohkura Y (1984) J Chromatogr 309:309–315. doi:10.1016/0378-4347(84)80038-9
Hsieh Y, Chen J (2005) Rapid Commun Mass Spectrom 19:3031–3036. doi:10.1002/rcm.2171
Pfuhl P, Kärcher U, Häring N, Baumeister A, Schubert-Zsilavecz M (2005) J Pharm Biomed Anal 36:1045–1052. doi:10.1016/j.jpba.2004.08.033
Cuadros-Rodríguez L, Bagur-González MG, Sánchez-Viñas M, González-Casado A, Gómez-Sáez AM (2007) J Chromatogr A 1158:33–46. doi:10.1016/j.chroma.2007.03.030
Lang R, Yagar EF, Eggers R, Hofmann T (2008) J Agric Food Chem 56:11114–11121. doi:10.1021/jf802838s
Guidelines for industry: bioanalytical method validation, US Department for Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER) (2001) http://www.fda.gov/cder/guidance/4252fnl.pdf
Miyauchi Y, Sano N, Nakamura T (1993) Int J Vitam Nutr Res 63:145–149
Davidson MH, Lukacsko P, Sun JX, Phillips G, Walters E, Sterman A, Niecestro R, Friedhoff L (2002) Clin Ther 24:112–125. doi:10.1016/S0149-2918(02)85009-3
Menon R, Tolbert D, Cefali E (2007) Biopharm Drug Dispos 28:297–306. doi:10.1002/bdd.555
Kos Pharmaceuticals, Inc. Advicor® (niacin extended-release/lovastatin tablets) (2006) http://www.advicor.com/important-safety-information.asp
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Min Song should be considered as co-first author.
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Wang, Y., Song, M., Hang, T. et al. LC-MS–MS Simultaneous Determination of Niacin, Niacinamide and Nicotinuric Acid in Human Plasma LC-MS–MS and Its Application to a Human Pharmacokinetic Study. Chroma 72, 245–253 (2010). https://doi.org/10.1365/s10337-010-1645-3
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DOI: https://doi.org/10.1365/s10337-010-1645-3