title: Determination of the cardioactive prototype LASSBio-294 and its metabolites in dog plasma by LC-MS/MS: application for a pharmacokinetic study.
abstract: In this work we describe the evaluation of the pharmacokinetics of a novel cardioactive compound of the N-acylhydrazone class, LASSBio-294, using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in dog plasma for the first time. Separation was achieved on a ZORBAX Rapid Resolution High Definition (RRHD) SB-C18 (50mm×2.1mm, 1.8μm) reversed-phase column at 20°C with methanol-10mM ammonium acetate solution (65:35, v/v) at a flow rate of 1.0mL/min. Detection was performed using an electrospray ionization (ESI) operating in positive ion multiple reaction monitoring (MRM) mode by monitoring the ion transitions from m/z 275.2→149.1 (LASSBio-294) and m/z 152.0→110.0 (acetaminophen, internal standard). The calibration curve of LASSBio-294 in plasma showed good linearity over the concentration range of 1.25-800ng/mL. The validated method was successfully applied to a pre-clinical pharmacokinetic study of the cardioactive prototype LASSBio-294 in beagles after oral administration. The main pharmacokinetic parameters t(1/2), C(max) and AUC(0-24) were (5.74±0.55)h, (547.66±35.12)ng/mL and (1621.77±41.66)ngh/mL, respectively.
authors: LaBioCon, Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia, GO, Brazil. valeria@farmacia.ufg.br
authors: Rodolpho C
authors: RC
authors: Braga
authors: Andréa C B
authors: AC
authors: Tôrres
authors: Camille B
authors: CB
authors: Persiano
authors: Rosângela O
authors: RO
authors: Alves
authors: Carlos A M
authors: CA
authors: Fraga
authors: Eliezer J
authors: EJ
authors: Barreiro
authors: Valéria
authors: V
authors: de Oliveira
mesh_terms: D000085:Acetates / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001798:Blood Proteins / Q000378:metabolism*; D002138:Calibration; D002317:Cardiovascular Agents / Q000032:analysis*; D002623:Chemistry Techniques, Analytical / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D006835:Hydrazones / Q000032:analysis*; D013058:Mass Spectrometry / Q000379:methods; D000432:Methanol / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000032:analysis; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013696:Temperature; D013876:Thiophenes / Q000032:analysis*
chemical_list: D000085:Acetates; D001798:Blood Proteins; D002317:Cardiovascular Agents; D006835:Hydrazones; C439284:LASSBio 294; D004364:Pharmaceutical Preparations; D013876:Thiophenes; C018824:ammonium acetate; D000432:Methanol