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 μL was injected onto the column for analysis. The LC/MS assay was linear over a BSH plasma concentration range of 20−0.5 μg/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 mL/min and the harmonic mean terminal half-life was 3.6 h.

Sensitivity enhancement in liquid chromatography/atmospheric pressure ionization mass spectrometry using derivatization and mobile phase additives

“…Most of the applications of volatile ion-pairing reagents with LC/MS have been limited to biomolecules such as oligonucleotides and amino acids. Triethylamine, tri-n-butylamine, and tetrabutylammonium acetate are the most commonly used ion-pairing reagents for native or chemically modified oligonucleotides and other anions in the negative detection mode [91][92][93]. The concentrations of amine additives are generally several mM in the mobile phase.…”

Boron neutron capture therapy assisted by boron-conjugated nanoparticles

“…However, because these compounds are rapidly cleared from the bloodstream (the half-life of blood-circulation time of BSH and boronophenylalanine is t 1/2 o1 h), 14,15 a high dose of 10 B-compounds is generally required to allow a sufficient concentration of 10 B atoms to accumulate in a tumor region. Therefore, the therapeutic value of cancer BNCT under in vivo conditions is largely dependent on the development of effective boron carrier systems that can achieve modulated disposition in the body through the intravenous route and facilitate accumulation in the tumor region.…”

LC–ESI-Q-TOF-MS for faster and accurate determination of microcystins and nodularins in serum

“…With the help of high accuracy mass, analytes have been detected in milk [22], urine [24], water samples and dietary supplements [25], and hair [26]. Plasma has been studied with TOF-MS instrumentation [27,28], but in these studies the quantitation is not based on accurate mass. For microcystin analysis, a TOF instrument has been used mainly for structural analysis [29][30][31] and for quantitative purposes [25,32].…”