title: Simultaneous determination of BNP7787 and its metabolite mesna in plasma and tissue by micro-HPLC with a dual electrochemical detector.
abstract: Sensitive, accurate, and precise assays are described to determine BNP7787 (disodium 2,2'-dithio-bis-ethane sulfonate) and its metabolite mesna (sodium 2-mercaptoethane sulfonate) simultaneously in plasma and tissue by micro-high-performance liquid chromatography (HPLC) with dual electrochemical detection. After separation of BNP7787 and mesna by micro-HPLC, the disulfide BNP7787 was reduced to mesna by a reactor cell with a glassy carbon working electrode (-1.6 V versus Hy-REF). At the second electrode, which consisted of a gold wall-jet electrode, the mesna generated from BNP7787 and the mesna already present in the samples were detected (+0.85 V versus Ag/AgCl). The lower limit of quantification (LLQ) of both compounds was 3 microM in plasma and 20 nmol/g in tissue. The dynamic range of the assay in plasma was 3-120 microM for mesna and 15-1200 microM for BNP7787. In tissue, the dynamic range was 20-2000 nmol/g for both compounds. The recovery of mesna from plasma and tissue ranged from 61.4 to 90.5% and 82.7 to 90.2%, respectively, and seemed to be concentration dependent. The recovery of BNP7787 from plasma and tissue was complete (i.e., 101.5 and 96.4%, respectively). The within- and between-day accuracy and precision for the plasma and tissue assay were within 14 and 7%, respectively. The utility of the assay was shown by determination of the stability of mesna and BNP7787 in a kidney sample of a rat and by analysis of plasma samples obtained from a patient receiving 18.4 g/m(2) BNP7787 as a 15-min intravenous infusion.
authors.affiliation: Department of Medical Oncology, Vrije Universiteit Medical Center, KRIGO, BR 232 De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands. M.Verschraagen@vumc.nl
authors.forename: Miranda
authors.initials: M
authors.lastname: Verschraagen
authors.forename: T H Ursula
authors.initials: TH
authors.lastname: Zwiers
authors.forename: Emine
authors.initials: E
authors.lastname: Torun
authors.forename: Martin G
authors.initials: MG
authors.lastname: Donker
authors.forename: Nico J
authors.initials: NJ
authors.lastname: Reinhoud
authors.forename: Wim J F
authors.initials: WJ
authors.lastname: Van der Vijgh
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism; D015080:Mesna / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D020011:Protective Agents / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D020011:Protective Agents; C027032:2,2'-dithiodiethanesulfonic acid; D015080:Mesna