Compendial testing of antiretroviral drug reference standards for metrologic traceability: Bictegravir and cabotegravir

Abstract

ISO/IEC 17043:2015 specifies general requirements for the competence of providers and development and operation of proficiency testing schemes. As a requirement of ISO/IEC 17043:2015 accreditation, the Clinical Pharmacology Quality Assurance (CPQA) program uses ISO 17034 certified reference materials (CRMs) to produce proficiency testing materials in antiretroviral drug panels. CRMs that meet the ISO/IEC 17034 standard can be prohibitively expensive for CPQA participating laboratories (CPLs), requiring authentication of purity and identity by compendial testing. Here, to assist CPLs, we report on a compendial testing approach used to assess whether standard reference materials for bictegravir and cabotegravir, two commonly prescribed drugs used in combination regimens in the treatment of HIV-1 infection, for proficiency testing. Our approach uses high-performance liquid chromatography and thermogravimetric analysis to evaluate purity of the materials, and the combination of high-resolution mass spectrometry and proton nuclear magnetic resonance spectroscopy to establish molecular identity. Using this workflow, we identified standard reference materials for bictegravir and cabotegravir that are economical alternatives for CPLs.