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Bis(pinacolato)diboron (BPD) and tetrahydroxydiboron (BBA) are commonly used reagents in Suzuki-Miyaura coupling for the synthesis of many intermediates and active pharmaceutical ingredients (APIs). These reagents have tested Ames positive and are classified as mutagenic by the International Council for Harmonization (ICH), under the "Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk," M7 (ICH M7) as Class 2 impurities. Because BPD and BBA are mutagenic, they need to be controlled and subsequently detected down to very low levels. Current methods using inductively coupled plasma-mass spectrometry (ICP-MS) give only the total boron content, which is problematic if the API also contains a boron molecule. In this paper, we describe a novel gas chromatography (GC)-MS approach for the low-level analysis of BPD and BBA in drug substances, even in the presence of boron from other sources. The analysis of BBA required derivatization of BPA to BPD, resulting in quantitation limits of 30 ppm of BBA (back calculated from the derivatized compound). BPD could be analyzed directly with quantitation limits of 2.5 ppm. [ABSTRACT FROM AUTHOR]