Compendial testing data of bictegravir and cabotegravir

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 Program uses ISO 17034 certified reference materials (CRMs) to produce proficiency testing materials. When CRMs that meet the ISO/IEC 17034 standard are not available or are prohibitively expensive, the purity and identity of non-certified standards must be authenticated by compendial testing to establish fit for intended use. Here, we report on a compendial testing approach used to assess whether standard reference materials for bictegravir and cabotegravir, two emerging drugs used in the treatment of HIV infection, are suitable for proficiency testing. Our approach uses high performance liquid chromatography and thermogravimetric analysis to evaluate purity of the materials and high-resolution mass spectrometry and proton nuclear magnetic resonance spectroscopy to establish molecular identity. Using this approach, we were able to certify standard reference materials for bictegravir and cabotegravir that are suitable for proficiency testing, providing some lower-costs alternatives.

Methods
HPLC experiments were conducted on a Shimadzu Prominence HPLC with PDA detection. Chromatograms were integrated and retention times, peak areas, and area percentages were recorded using the Shimadzu software.

Thermogravimetric analysis has conducted on PerkinElmer TGA 8000. Sampling data was downloaded into a .csv file and processed in Microsoft Excel.

High-resolution mass spectrometry analysis was conducted on a ThermoFisher Q Exactive Orbitrap mass spectrometer and the .RAW data files processed using XCalibur.

Proton nuclear magnetic resonance analysis was conducted on a Bruker Avance NEO 400 MHz run with TopSpin software, and data were processed using the Mnova software from Mestrelab Research.