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Miniature mass spectrometer–based point-of-care assay for cabotegravir and rilpivirine in whole blood

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Abstract

HIV prevention and treatment with injectable cabotegravir and/or rilpivirine administered once every 4 to 8 weeks is an attractive alternative to daily therapy. Prescribed dosage and drug concentrations in plasma are based on patient data collected in clinical trials, but actual patients are expected to exhibit more variability in drug concentrations, which is important to quantify. Here, we demonstrate the first quantitative point-of-care assay with a miniature mass spectrometer to assess these drug concentrations in whole blood. Quantitative performance is obtained using paper spray ionization in combination with tandem mass spectrometry (MS/MS) in the clinically relevant concentration range of both drugs. Limits of quantitation (LoQs) of cabotegravir and rilpivirine are measured to be 750 ng/mL and 20 ng/mL, respectively. The assay turnaround time is < 4 min, and strong linear relationships are established between MS/MS responses and concentration, with percentage of relative standard deviations (RSDs) that are <15% at concentrations above the LoQs. The speed, portability, low power consumption, and specificity offered by the miniature instrument should make it an appropriate platform for measuring drug concentrations in a walk-in clinic using small volumes of patient blood.

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Acknowledgements

The authors thank Mark Carlsen of the Jonathan Amy Facility for Chemical Instrumentation for electronics support. The authors also thank Lucas J. Szalwinski and Robert L. Schrader for assistance with instrumentation.

Funding

We acknowledge funding to P.L.A. from the National Institute of Health under the award number R01AI122298. The authors also acknowledge support from Teledyne FLIR under FLIR Basic Research Award #18057244.

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Authors and Affiliations

  1. Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA

    Sangeeta Pandey, Yanyang Hu & R. Graham Cooks

  2. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, 80045, USA

    Lane R. Bushman & Peter L. Anderson

  3. Division of Infectious Diseases, School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO, 80045, USA

    Jose Castillo-Mancilla

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  1. Sangeeta Pandey
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Correspondence to Peter L. Anderson or R. Graham Cooks.

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Pandey, S., Hu, Y., Bushman, L.R. et al. Miniature mass spectrometer–based point-of-care assay for cabotegravir and rilpivirine in whole blood. Anal Bioanal Chem 414, 3387–3395 (2022). https://doi.org/10.1007/s00216-022-03954-3

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