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Development and validation of a multiplex UHPLC-MS/MS assay with stable isotopic internal standards for the monitoring of the plasma concentrations of the antiretroviral drugs bictegravir, cabotegravir, doravirine, and rilpivirine in people living with HIV
- Source :
- Journal of Mass Spectrometry, Journal of mass spectrometry, vol. 55, no. 6, pp. e4506
- Publication Year :
- 2020
-
Abstract
- The widespread use of highly active antiretroviral treatments has dramatically changed the prognosis of people living with HIV (PLWH). However, such treatments have to be taken lifelong raising issues regarding the maintenance of both therapeutic effectiveness and long‐term tolerability. Recently approved or investigational antiretroviral drugs present considerable advantages, allowing once daily oral dosage along with activity against resistant variants (eg, bictegravir and doravirine) and also parenteral intramuscular administration that facilitates treatment adherence (eg, long‐acting injectable formulations such as cabotegravir and rilpivirine). Still, there remains a risk of insufficient or exaggerated circulating exposure due to absorption issues, abnormal elimination, drug‐drug interactions, and others. In this context, a multiplex ultra‐high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC‐MS/MS) bioassay has been developed for the monitoring of plasma levels of bictegravir, cabotegravir, doravirine, and rilpivirine in PLWH. A simple and convenient protein precipitation was performed followed by direct injection of the supernatant into the UHPLC‐MS/MS system. The four analytes were eluted in less than 3 minutes using a reversed‐phase chromatography method coupled with triple quadrupole mass spectrometry detection. This bioassay was fully validated following international guidelines and achieved good performances in terms of trueness (94.7%‐107.5%), repeatability (2.6%‐11%), and intermediate precision (3.0%‐11.2%) over the clinically relevant concentration ranges (from 30 to 9000 ng/mL for bictegravir, cabotegravir, and doravirine and from 10 to 1800 ng/mL for rilpivirine). This sensitive, accurate, and rapid UHPLC‐MS/MS assay is currently applied in our laboratory for routine therapeutic drug monitoring of the oral drugs bictegravir and doravirine and is also intended to be applied for the monitoring of cabotegravir/rilpivirine levels in plasma from PLWH receiving once monthly or every 2‐month intramuscular injection of these long‐acting antiretroviral drugs.
- Subjects :
- 10028 Institute of Medical Virology
UHPLC-MS/MS
antiretroviral therapy
long-acting injectables
pharmacokinetics
therapeutic drug monitoring
Pyridones
UHPLC‐MS/MS
1607 Spectroscopy
Context (language use)
610 Medicine & health
HIV Infections
Pharmacology
01 natural sciences
Heterocyclic Compounds, 4 or More Rings
Piperazines
10234 Clinic for Infectious Diseases
long‐acting injectables
chemistry.chemical_compound
Cabotegravir
Pharmacokinetics
Limit of Detection
Tandem Mass Spectrometry
medicine
Humans
Multiplex
Spectroscopy
Chromatography, High Pressure Liquid
Research Articles
medicine.diagnostic_test
Bictegravir
010405 organic chemistry
010401 analytical chemistry
Rilpivirine
Reproducibility of Results
Reference Standards
Triazoles
Amides
0104 chemical sciences
chemistry
Tolerability
Anti-Retroviral Agents
Therapeutic drug monitoring
Linear Models
Drug Monitoring
Heterocyclic Compounds, 3-Ring
Research Article
Subjects
Details
- ISSN :
- 10969888
- Volume :
- 55
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of mass spectrometry : JMS
- Accession number :
- edsair.doi.dedup.....0ac59cb6403871575ca83ee32d9b4592