title: Simultaneous determination of 1-β-d-Arabinofuranosylcytosine and two metabolites, 1-β-d-Arabinofuranosyluracil and 1-β-d-Arabinofuranosylcytosine triphosphate in leukemic cell by HPLC-MS/MS and the application to cell pharmacokinetics.
abstract: A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of 1-β-d-Arabinofuranosylcytosine (ara-C), 1-β-d-Arabinofuranosyluracil (ara-U) and 1-β-d-Arabinofuranosylcytosine triphosphate (ara-CTP) in the leukemic cells for the first time. The analytes were separated on a C18 column (100mm×2.1mm, 1.8μm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was used for detection. The ion-pairing reagent, NFPA, was added to the mobile phase to retain the analytes in the column. The cell homogenates sample was prepared by the simple protein precipitation. The calibration curves were linear over a concentration range of 3.45-3450.0ng/mL for ara-C, 1.12-1120.0ng/mL for ara-U and 4.13-4130.0ng/mL for ara-CTP. The intra-day and inter-day precision was less than 15% and the relative error (RE) were all within ±15%. The validated method was successfully applied to assess the disposition characteristics of ara-C and support cell pharmacokinetics after the patients with leukemia were intravenously infused with SDAC and HiDAC. The result of the present study would provide the valuable information for the ara-C therapy.
authors.affiliation: College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang Distrct, Harbin 150081, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liang
authors.affiliation: Department of Infectious Diseases, the Second Affiliated Hospital, Harbin Medical University, No. 246 Xuefu Road, Nangang Distrct, Harbin 150086, China. Electronic address: doctor.wangwei@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang Distrct, Harbin 150081, China.
authors.forename: Xuechun
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, School of Basic Medical Sciences, Shenyang Medical College, No. 146 Huanghebei Street, Huanggu District, Shenyang 110034, China.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Yin
mesh_terms: D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D001085:Arabinofuranosylcytosine Triphosphate / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D001086:Arabinofuranosyluracil / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003561:Cytarabine / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D057230:Limit of Detection; D008875:Middle Aged; D053719:Tandem Mass Spectrometry / Q000379:methods; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate; D001086:Arabinofuranosyluracil
keywords: Ara-C; Ara-CTP; Ara-U; Cell pharmacokinetics; HPLC-MS/MS