title: A rapid and highly sensitive UPLC-MS/MS method using pre-column derivatization with 2-picolylamine for intravenous and percutaneous pharmacokinetics of valproic acid in rats.
abstract: A rapid, highly sensitive and specific ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for the detection of valproic acid (VPA) in rat plasma following the topical application was developed and validated. This method was carried out with pre-column derivatization using 2-picolylamine (PA) which reacts with the carboxylic acid group of VPA. The derivatization was completed in 10min and the resulting PA-VPA derivative enabled the sensitive detection of VPA in selected reaction monitoring (SRM) mode. Sample preparation was done with simple liquid-liquid extraction and chromatographic separation was achieved within 5min on a C18 column using a gradient elution with the mobile phase of 2mM ammonium formate containing 0.1% formic acid and methanol. The standard curves were linear over the concentration range of 0.07-200μg/mL with a correlation coefficient higher than 0.99. The limit of detection (LOD) and the lower limit of quantification (LLOQ) was 0.03 and 0.07μg/mL, respectively with 100μL of plasma sample. The intra- and inter-day precisions were measured to be below 10.7% and accuracies were within the range of 94.1-115.9%. The validated method was successfully applied to the pharmacokinetics of VPA in the rat following topical and intravenous applications.
authors.affiliation: AMOREPACIFIC CO/R&D Center, Gyeonggi-do 446-729, Republic of Korea.
authors.forename: Kyung-Mi
authors.initials: KM
authors.lastname: Joo
authors.forename: Dalwoong
authors.initials: D
authors.lastname: Choi
authors.forename: Yang-Hui
authors.initials: YH
authors.lastname: Park
authors.forename: Chang-Geun
authors.initials: CG
authors.lastname: Yi
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Jun-Cheol
authors.initials: JC
authors.lastname: Cho
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lim
mesh_terms: D061605:Administration, Intravenous; D000287:Administration, Topical; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D057230:Limit of Detection; D008297:Male; D017711:Nonlinear Dynamics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D014635:Valproic Acid
keywords: 2-Picolylamine; Derivatization; Pharmacokinetics; Topical application; UPLC–MS/MS; Valproic acid