Development and Validation of a Liquid Chromatography Coupled to Tandem Mass Spectrometry Method for the Monitoring of Temsavir Plasma Concentrations in People Living with HIV

Posted: 9 Dec 2022

See all articles by Paul Thoueille

Paul Thoueille

University of Lausanne - Lausanne University Hospital

Ulrich Seybold

University of Lausanne - Lausanne University Hospital; German Center of Infection Research (DZIF)

Laurent Arthur Decosterd

University of Lausanne - Laboratory of Clinical Pharmacology

Vincent Desfontaine

University of Lausanne - Lausanne University Hospital

Abstract

A majority of people living with HIV (PLWH) now have access to HIV treatment with high antiviral potency and favorable tolerability profile. However, in some treatment experienced PLWH viral strains resistant to major current classes of antiretrovirals have emerged, usually due to periods with continued virus replication in the presence of failing drug regimens and thus selection pressure. In such context, new treatment options are therefore needed.Fostemsavir (RUKOBIA®) is the prodrug of temsavir, a first-in-class oral attachment inhibitor approved for the treatment of heavily treatment-experienced adults with multidrug-resistant HIV-1 infection. In this case RUKOBIA® is part of a complex regimen of antiretroviral drugs, often in addition to other drugs for chronic co-morbidities (e.g., heart disease, diabetes mellitus, hepatic and renal impairment, etc). In such a multi-drug regimen context, therapeutic drug monitoring (TDM) of temsavir can be necessary to exclude or adjust for relevant drug-drug interactions. A highly selective assay by liquid chromatography method coupled to tandem mass spectrometry (LC-MS/MS) was therefore developed for the quantification of temsavir in human plasma. A convenient sample preparation using protein precipitation with acetonitrile followed by supernatant dilution was carried out. Temsavir and fostemsavir were separated in less than 2 minutes using a multi-step UPLC gradient, thus ensuring adequate quantification of temsavir. The assay for the quantification of temsavir was extensively validated over the large range of clinically relevant concentrations from 1 to 10’000 ng/mL, in accordance with international bioanalytical method guidelines. The method achieves excellent performance in terms of trueness (99.7 to 105.3%), repeatability and intermediate precision (both from 1.6% to 5.8%).This LC-MS/MS method is now part of the routine analyses of the Laboratory of the Service of Clinical Pharmacology of Lausanne (CHUV), Switzerland, as an integrated part of our general TDM Service for antiretrovirals.

Note:
Funding Declaration: This work was supported by the Swiss National Science Foundation, grant number N° 324730_192449 (to L.A.D).

Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical Approval: According to Swiss Law and Institutional rules, ethical approval is not required for a retrospective case report involving anonymised clinical data (see the Federal Act on Research involving Human Beings [15]).

Keywords: Temsavir, Fostemsavir, LC-MS/MS, Therapeutic Drug Monitoring, HIV

Suggested Citation

Thoueille, Paul and Seybold, Ulrich and Decosterd, Laurent Arthur and Desfontaine, Vincent, Development and Validation of a Liquid Chromatography Coupled to Tandem Mass Spectrometry Method for the Monitoring of Temsavir Plasma Concentrations in People Living with HIV. Available at SSRN: https://ssrn.com/abstract=4281592

Paul Thoueille (Contact Author)

University of Lausanne - Lausanne University Hospital ( email )

Ulrich Seybold

University of Lausanne - Lausanne University Hospital ( email )

German Center of Infection Research (DZIF) ( email )

Laurent Arthur Decosterd

University of Lausanne - Laboratory of Clinical Pharmacology ( email )

Quartier Chambronne
Lausanne, Vaud CH-1015
Switzerland

Vincent Desfontaine

University of Lausanne - Lausanne University Hospital ( email )

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