Determination of the cardioactive prototype LASSBio-294 and its metabolites in dog plasma by LC-MS/MS: Application for a pharmacokinetic study

作者：Braga Rodolpho C; Torres Andrea C B; Persiano Camille B; Alves Rosangela O; Fraga Carlos A M; Barreiro Eliezer J; de Oliveira Valeria^*

来源：Journal of Pharmaceutical and Biomedical Analysis, 2011, 55(5): 1024-1030.

DOI：10.1016/j.jpba.2011.02.031

• LASSBio-294
• LC-MS/MS
• Pharmacokinetics
• Canine plasma
• Oral administration

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) 58-08 (50 mm x 2.1 mm. 1.8 mu m) reversed-phase column at 20 degrees C with methanol-10 mM ammonium acetate solution (65:35, v/v) at a flow rate of 1.0 mL/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 1.25-800 ng/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)ng h/mL, respectively.

• 出版日期2011-7-15