title: Reduction of carry-over in column-switching HPLC/MS system with automated system washing procedure for highly sensitive direct analysis of donepezil in dog plasma.
abstract: To solve the problem of carry-over--a persistent chromatographic challenge for bioanalytical assays with highly sensitive detector such as a mass spectrometry (MS)--a new on-line sample pretreatment HPLC/MS system using a column-switching technique was established. This system was designed to reduce carry-over based on a hydrophobic interaction mechanism using a washing function (multi-mobile phase flow system), as well as to remove impurities on-line in a mobile phase for the pretreatment. As a result, a washing function in this system was enabled to reduce carry-over and to remove impurities in a mobile phase by automatic operation. Therefore, concentration levels of donepezil (DH) in dog plasma as low as 10 pg/mL could be determined using this on-line sample pretreatment HPLC/MS system. In addition, method validation results of specificity, linearity, accuracy, precision, lower limit of quantitation (LLOQ), and carry-over demonstrated that this on-line sample pretreatment HPLC/MS system was robust and valid as a practical assay of drugs and metabolites in the biological samples.
authors.affiliation: Sunplanet Co., Ltd., 2 Kawashimatakehaya, Kakamigahara, Gifu 501-6024, Japan. y-asakawa-sun@hhc.eisai.co.jp
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Asakawa
authors.forename: Chinami
authors.initials: C
authors.lastname: Ozawa
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Osada
authors.forename: Shoji
authors.initials: S
authors.lastname: Kaneko
authors.forename: Naoki
authors.initials: N
authors.lastname: Asakawa
mesh_terms: D000818:Animals; D001322:Autoanalysis / Q000379:methods; D002800:Cholinesterase Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D004285:Dogs; D000077265:Donepezil; D007189:Indans / Q000097:blood* / Q000493:pharmacokinetics; D016014:Linear Models; D010880:Piperidines / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil