title: A full validated hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the quantification of oxaliplatin in human plasma ultrafiltrates.
abstract: Oxaliplatin is a platinum agent that is used for treatment of colorectal cancer. A sensitive and selective hydrophilic interaction liquid chromatography-tandem mass spectrometric method for the quantification of oxaliplatin was developed. Human plasma ultrafiltrates were precipitated by acetonitrile containing carboplatin as an internal standard and further diluted with acetonitrile. Chromatographic separation of oxaliplatin and the internal standard was achieved with a column modified with phosphorylcholine and an isocratic mobile phase (acetonitrile/water/acetic acid=90:10:0.1, v/v/v) at the flow rate of 0.2mL/min. The lower limit of quantification for oxaliplatin was 25ng/mL. The linearity range of the method was from 25 to 5000ng/mL. The intra-day precision and inter-day precision (RSD) ranged from 0.8 to 6.1%, and the accuracy (RE) was within ±4.5%. The extraction recoveries from human plasma ultrafiltrates were 83.6-91.6%, and ion suppression caused by matrix components was 86.7-88.5% at three different levels, respectively. This method was applied to a clinical pharmacokinetic study of oxaliplatin in a cancer patient. The maximum concentration of colorectal cancer patient administered oxaliplatin was 1650ng/mL.
authors.affiliation: Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Ito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Asuka
authors.initials: A
authors.lastname: Fujikawa
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Ayako
authors.initials: A
authors.lastname: Furugen
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Miyamori
authors.forename: Natsuko
authors.initials: N
authors.lastname: Takahashi
authors.forename: Jiro
authors.initials: J
authors.lastname: Ogura
authors.forename: Masaki
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Nariyasu
authors.initials: N
authors.lastname: Mano
authors.forename: Ken
authors.initials: K
authors.lastname: Iseki
mesh_terms: D000097:Acetonitriles / Q000737:chemistry; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009944:Organoplatinum Compounds / Q000097:blood* / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D010767:Phosphorylcholine / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014462:Ultrafiltration
chemical_list: D000097:Acetonitriles; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010767:Phosphorylcholine; C032159:acetonitrile