Direct quantitation of tenofovir diphosphate in human blood with mass spectrometry for adherence monitoring

Inadequate adherence to chronic medications is a far-reaching problem with financial and human health consequences. By a wide margin, non-adherence is the leading cause of therapeutic failures of HIV pre-exposure chemoprophylaxis (PrEP) and antiretroviral therapy (ART). It has been proven that HIV i...

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Bibliographic Details
Published in:Analytical and bioanalytical chemistry 2020-02, Vol.412 (6), p.1243-1249
Main Authors: Pu, Fan, Pandey, Sangeeta, Bushman, Lane R., Anderson, Peter L., Ouyang, Zheng, Cooks, R. Graham
Format: Article
Language:English
Subjects:
Adenine - analogs & derivatives
Adenine - blood
Adenine - standards
Analysis
Analytical Chemistry
Anti-HIV Agents - administration & dosage
Anti-HIV Agents - blood
Anti-HIV Agents - standards
Antiretroviral agents
Antiretroviral drugs
Antiretroviral therapy
Biochemistry
Blood
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Chromatography, Liquid - methods
Communication
Desalination
Emtricitabine
Erythrocytes
Food Science
HIV
Human immunodeficiency virus
Humans
Intracellular
Laboratory Medicine
Mass spectrometers
Mass spectrometry
Mass spectroscopy
Methods
Monitoring
Monitoring/Environmental Analysis
Organophosphates - blood
Organophosphates - standards
Patient compliance
Proof of Concept Study
Quadrupoles
Quantitation
Reference Standards
Spectrometers
Tandem Mass Spectrometry - methods
Tenofovir
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Summary:Inadequate adherence to chronic medications is a far-reaching problem with financial and human health consequences. By a wide margin, non-adherence is the leading cause of therapeutic failures of HIV pre-exposure chemoprophylaxis (PrEP) and antiretroviral therapy (ART). It has been proven that HIV infection can be prevented by daily dosing of emtricitabine and tenofovir disoproxil fumarate. Measurement of intracellular tenofovir diphosphate in red blood cells has been established as an effective way to assess cumulative adherence, however, the LC-MS-based analytical method developed for the purpose is both complicated and expensive. Here, we report a simple method for adherence monitoring based on direct MS quantification of intracellular tenofovir diphosphate in human whole blood. The method requires only microliters of whole blood, employs special membranes to perform plasma separation and concomitant desalting during blood collection, and uses nanoelectrospray on a triple quadrupole instrument. Quantitative performance in this proof-of-concept study includes RSDs of
ISSN:1618-2642
1618-2650
DOI:10.1007/s00216-019-02304-0