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

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 55; no. 5; pp. 1024 - 1030
• Main Authors: Braga, Rodolpho C., Tôrres, Andréa C.B., Persiano, Camille B., Alves, Rosângela O., Fraga, Carlos A.M., Barreiro, Eliezer J., de Oliveira, Valéria
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-07-2011; Elsevier
• Subjects: acetaminophen; Acetates - chemistry; Administration, Oral; ammonium acetate; Analysis; Analytical, structural and metabolic biochemistry; Animals; Area Under Curve; Beagle; Biological and medical sciences; Blood Proteins - metabolism; Calibration; Canine plasma; Cardiovascular Agents - analysis; Chemistry Techniques, Analytical - methods; Chemistry, Pharmaceutical - methods; Chromatography, High Pressure Liquid - methods; Chromatography, Liquid - methods; Dogs; Fundamental and applied biological sciences. Psychology; General pharmacology; Hydrazones - analysis; ionization; LASSBio-294; LC–MS/MS; liquid chromatography; Mass Spectrometry - methods; Medical sciences; metabolites; Methanol - chemistry; monitoring; Oral administration; Pharmaceutical Preparations - analysis; Pharmacokinetics; Pharmacology. Drug treatments; Reproducibility of Results; tandem mass spectrometry; Tandem Mass Spectrometry - methods; Temperature; Thiophenes - analysis; Canine plasma; Pharmacokinetics; LC–MS/MS; LASSBio-294; Oral administration; Fissipedia; Biological fluid; Carnivora; Prototype; Metabolite; HPLC chromatography; Determination; Blood plasma; LC-MS/MS; Vertebrata; Mammalia; Animal; Mass spectrometry MS/MS; Dog; Quantitative analysis
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2011.02.031

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 (50
mm
×
2.1
mm, 1.8
μm) reversed-phase column at 20
°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.