Quantitation of imidazo[1,2-a]quinoxaline derivatives in human and rat plasma using LC/ESI-MS.
Since several years, our group developed quinoxalinic compounds. Among the synthesized compounds, in the imidazo[1,2-a]quinoxaline series, EAPB0203 has shown interesting activities both on melanoma and lymphoma. The structure of EAPB0203 has been modulated and a new compound, EAPB0503, exhibits an in vitro cytotoxic activity on melanoma cancer cell line 7-9 times higher than EAPB0203. We validated an LC/ESI-MS method to simultaneously quantify EAPB0503 and its metabolite EAPB0603 in human and rat plasma. Chromatography was performed on a C8 Zorbax eclipse XDB column with a mobile phase consisting of acetronitrile and formate buffer gradient elution. LC-MS data were acquired in SIM mode at m/z 305, 291, and 303 for EAPB0503, EAPB0603, and the internal standard, respectively. The drug/internal standard peak area ratios were linked via quadratic relationships to concentrations (low range: 5-300 microg/L, high range: 100-1000 microg/L). The method is precise (precision, < or = 14%) and accurate (recovery, 92-113%). Mean extraction efficiencies, > 72% for each analyte, were obtained. The lower LOQs were 5 microg/L. This highly specific and sensitive method was successfully used to investigate plasma concentrations of EAPB0503 and EAPB0603 in a pharmacokinetic study carried out in rat and would also be useful in clinical trials at a later stage.
Khier
Sonia
S
Clinical Pharmacokinetic Laboratory, EA4215, Faculty of Pharmacy, University Montpellier I, France.
Moarbess
Georges
G
Deleuze-Masquefa
Carine
C
Solassol
Isabelle
I
Margout
Delphine
D
Pinguet
Frédéric
F
Bonnet
Pierre-Antoine
PA
Bressolle
Françoise M M
FM
D000818:Animals; D002853:Chromatography, Liquid; D004355:Drug Stability; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D015394:Molecular Structure; D011810:Quinoxalines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization
D007093:Imidazoles; D011810:Quinoxalines