Abstract
Bis(pinacolato)diboron (B2Pin2) is a common reagent used to prepare pinacolboronate esters for Suzuki-Miyaura coupling reactions in pharmaceutical syntheses. As a known mutagenic impurity, it is challenging to develop analytical methods for the determination of B2Pin2 due to its low control limit, high reactivity, and lack of chromophore. Here, we report a generic liquid chromatography (LC)- mass spectrometry (MS) method to monitor B2Pin2 at low parts per million (ppm) levels in pharmaceutical compounds by single ion monitoring. Ammonium acetate (0.5 mM) was added in the mobile phases to form B2Pin2 gas-phase ammonium adduct, which eliminated MS instrumentation variances and achieved a quantification limit (QL) better than 10 ng/mL (corresponding to 1 ppm in substrate at 10 mg/mL) with optimized LC conditions. To accommodate diverse solubility profiles of pharmaceutical compounds, three diluents including acetonitrile, stabilized tetrahydrofuran, and dimethyl sulfoxide were recommended as the primary diluents based on B2Pin2 solution stability. Three alternative diluents with additives were proposed as backups. Three Bristol Myers Squibb compounds that required B2Pin2 control were spiked with 1–20 ppm B2Pin2 as the case studies. The QLs for all three materials were better than 1 ppm and the recovery values were within 100 ± 20% at 1, 10, and 20 ppm spiked levels.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
