title: Validation of the LC-MS/MS method for the quantification of mevalonic acid in human plasma and determination of the matrix effect.
abstract: A simple, specific, and sufficiently sensitive liquid chromatography-tandem mass spectrometry (negative-ion electrospray ionization) methodology to determine mevalonic acid (MVA) in human plasma is described, and its application to the analysis of rat plasma MVA levels after rosuvastatin administration is demonstrated. The method was validated over the linearity range of 0.5-50.0 ng/ml (r(2) > 0.99) using deuterated MVA as an internal standard. The lower limit of quantification was 0.5 ng/ml. The assay procedure involved the isolation of MVA from plasma samples using solid-phase extraction. Chromatographic separation was achieved on a HyPurity Advance column with a mobile phase consisting of ammonium formate buffer (10 mM, pH 8.0) and acetonitrile (70:30, v/v). Excellent precision and accuracy were observed. MVA and deuterated mevalonolactone were stable in water and plasma under different storage and processing conditions. The recovery observed was low, which was attributable to a significant matrix effect. A significant decrease (30-40%; P < 0.05) was observed in rat plasma MVA levels after rosuvastatin administration.
authors.affiliation: Department of Metabolism and Pharmacokinetics, Ranbaxy Research Laboratories, Jamia Hamdard, Delhi, India.
authors.forename: G S
authors.initials: GS
authors.lastname: Saini
authors.forename: T A
authors.initials: TA
authors.lastname: Wani
authors.forename: A
authors.initials: A
authors.lastname: Gautam
authors.forename: B
authors.initials: B
authors.lastname: Varshney
authors.forename: T
authors.initials: T
authors.lastname: Ahmed
authors.forename: K S
authors.initials: KS
authors.lastname: Rajan
authors.forename: K K
authors.initials: KK
authors.lastname: Pillai
authors.forename: J K
authors.initials: JK
authors.lastname: Paliwal
mesh_terms: D000818:Animals; D016477:Artifacts; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005464:Fluorobenzenes / Q000494:pharmacology; D006801:Humans; D013058:Mass Spectrometry / Q000592:standards*; D008798:Mevalonic Acid / Q000097:blood*; D008958:Models, Molecular; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D000068718:Rosuvastatin Calcium; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D005464:Fluorobenzenes; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D008798:Mevalonic Acid