Application of liquid chromatography-tandem mass spectrometry method for the simultaneous quantitative analysis of propentofylline and its chiral metabolite M1 in rats.
A sensitive and selective liquid chromatographic-electrospray ionization mass spectrometric method for the simultaneous determination of propentofylline and enantiomers of its active metabolite M1 in rat serum, cortex and hippocampus was developed and validated according to GLP procedures. Sample preparations were carried out by liquid-liquid extraction using diethyl ether after the addition of the internal standard (pentoxifylline). The dried residue was reconstituted in mobile phase and injected onto a Chiralpak AD column (10 µm, 250 × 4.6 mm i.d.). The limit of quantification for propentofylline in serum, cortex and hippocampus was set at 0.25 ng/mL and for enantiomers of its metabolite M1 at 1.25 ng/mL. The established LC/ESI-MS/MS method has been successfully applied to an initial pharmacokinetic study of propentofylline and also to assessment of distribution of parent drug and enantiomers of its pharmacologically active metabolite M1 to cortex and hippocampus after intravenous administration of propentofylline to rats at a dose of 5 mg/kg.
Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University Medical College, Kraków, Poland. mwalczak.farm@poczta.fm
Maria
M
Walczak
Ewelina
E
Kozaczek
Joanna
J
Szymura-Oleksiak
Elżbieta
E
Pękala
D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D008297:Male; D010431:Pentoxifylline / Q000032:analysis / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014970:Xanthines / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics
D014970:Xanthines; C032114:propentofylline; D010431:Pentoxifylline