title: Simple liquid chromatography method for the quantification of irinotecan and SN38 in sheep plasma: application to in vivo pharmacokinetics after pulmonary artery chemoembolization using drug eluting beads.
abstract: A rapid and simple liquid chromatography-fluorescence detection (LC-FD) method was developed and validated for the simultaneous quantification of irinotecan (CPT11) and SN38 in sheep plasma. Camptothecin (CPT) was used as the internal standard. A single step protein precipitation with acetonitrile was used for sample preparation. The separation was achieved using a 5 microm C18 column (250 mm x 4.5 mm, 5 microm) with a mobile phase composed of 36 mM sodium dihydrogen phosphate dehydrate and 4 mM sodium 1 heptane sulfonate-acetonitrile (72:28), the pH of the mobile phase was adjusted to 3. The flow rate was 1.45 mL/min and the fluorescence detection was operated at 355/515 nm (excitation/emission wavelengths). The run time was 13 min. The method was validated with respect to selectivity, extraction recovery, linearity, intra- and inter-day precision and accuracy, limit of quantification and stability. The method has a limit of quantification of 5 ng/mL for both CPT11 and SN38. The assay was linear over concentrations ranging from 5 to 5000 ng/mL and to 240 ng/mL for CPT11 and SN38, respectively. This method was used successfully to perform plasma pharmacokinetic studies of CPT11 after pulmonary artery embolization (PACE) in a sheep model. It was also validated for CPT11 and SN38 analysis in sheep lymph and human plasma.
authors.affiliation: EA 2706, Paris Sud-XI University, Châtenay-Malabry, France.
authors.forename: Minh-Tâm
authors.initials: MT
authors.lastname: Baylatry
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Joly
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pelage
authors.forename: Leila
authors.initials: L
authors.lastname: Bengrine-Lefevre
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Prugnaud
authors.forename: Alex
authors.initials: A
authors.lastname: Laurent
authors.forename: Christine
authors.initials: C
authors.lastname: Fernandez
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood* / Q000493:pharmacokinetics; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D016461:Chemoembolization, Therapeutic / Q000295:instrumentation*; D002853:Chromatography, Liquid / Q000379:methods*; D016503:Drug Delivery Systems; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D000077146:Irinotecan; D023421:Models, Animal; D011651:Pulmonary Artery / Q000187:drug effects*; D012756:Sheep
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C106003:SN38-Glu; D000077146:Irinotecan; D002166:Camptothecin