title: Electrospray ionization mass spectrometry coupled to reversed-phase ion-pair high-performance liquid chromatography for quantitation of sodium borocaptate and application to pharmacokinetic analysis.
abstract: We have developed a quantitative assay using electrospray ionization mass spectrometry coupled to reversed-phase ion-pair liquid chromatography (LC/MS) for quantitation of sodium borocaptate (BSH) in human plasma. The assay was developed using a Micromass Q-TOF II mass spectrometer equipped with an orthogonal electrospray source. The mobile phase was a 1:1 solution of methanol and 5 mM aqueous tetrabutylammonium acetate flowing at 0.2 mL/min, and the chromatography was performed using a Machery-Nagel Nucleosil C18 column. Plasma samples from patients who had received an intravenous infusion of sodium borocaptate (Na2B12H11SH), frequently referred to as BSH, were prepared for analysis by precipitation with acetonitrile. Following this, the supernatants were collected, and 40 microL was injected onto the column for analysis. The LC/MS assay was linear over a BSH plasma concentration range of 20-0.5 microg/mL with acceptable variability for both intra- and interassay precision. The LC/MS assay was used to generate pilot pharmacokinetic data for the plasma disposition of BSH in humans. The disposition of BSH was found to be consistent with a two-compartment model with first-order elimination from the central compartment. The mean total body plasma clearance was 95.7 +/- 30.8 m/min and the harmonic mean terminal half-life was 3.6 h.
authors.affiliation: College of Pharmacy, Department of Pathology, The Ohio State University, Columbus 43210, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Gibson
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Staubus
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Barth
authors.forename: Weilian
authors.initials: W
authors.lastname: Yang
authors.forename: Nan M
authors.initials: NM
authors.lastname: Kleinholz
authors.forename: R Benjamin
authors.initials: RB
authors.lastname: Jones
authors.forename: Kari B
authors.initials: KB
authors.lastname: Green-Church
authors.forename: Wemer
authors.initials: W
authors.lastname: Tjarks
authors.forename: Albert H
authors.initials: AH
authors.lastname: Soloway
mesh_terms: D001894:Borohydrides / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D016754:Boron Neutron Capture Therapy; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D006801:Humans; D008657:Metabolic Clearance Rate; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000295:instrumentation / Q000379:methods*; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D001894:Borohydrides; D013438:Sulfhydryl Compounds; C014651:mercaptoundecahydrododecaborate