Evidence map›Paper›PMID 24661980›Full record

ArticleClinica chimica acta; international journal of clinical chemistry2014

The development and validation of a method using high-resolution mass spectrometry (HRMS) for the qualitative detection of antiretroviral agents in human blood.

Mark A Marzinke, Autumn Breaud, Teresa L Parsons, Myron S Cohen, Estelle Piwowar-Manning, Susan H Eshleman, William Clarke

Open access · greenAbstract readValidation Study
In one paragraph

Article in Clinica chimica acta; international journal of clinical chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
3.1field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 54 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Mark A MarzinkeDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Autumn BreaudDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Teresa L ParsonsDepartment of Medicine, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Myron S CohenInstitute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Estelle Piwowar-ManningDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Susan H EshlemanDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
William ClarkeDepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: wclarke@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · USUniversity of North Carolina at Chapel Hill · US

Funding

LC: HIV Prevention Trials Network - Laboratory Support for the SARS-CoV-2 Seroprevalence Study (CoVPN 5002)UM1AI068613 · NIAID · JOHNS HOPKINS UNIVERSITY · PI SUSAN H ESHLEMAN, Mark A Marzinke · 2011 to 2026
$100.2M
HIV Prevention Trials Network: Network LaboratoryU01AI068613 · NIAID · JOHNS HOPKINS UNIVERSITY · PI ESHLEMAN, SUSAN H · 2006 to 2010
$16.5M
NIAID NIH HHS UM1 AI068613NIAID NIH HHS UM1-AI068613
6 · The paper itself

Abstract

backgroundAntiretroviral drugs are used for the treatment and prevention of HIV infection. Non-adherence to antiretroviral drug regimens can compromise their clinical efficacy and lead to emergence of drug-resistant HIV. Clinical trials evaluating antiretroviral regimens for HIV treatment and prevention can also be compromised by poor adherence and non-disclosed off-study antiretroviral drug use. This report describes the development and validation of a high throughput, qualitative method for the identification of antiretroviral drugs using high-resolution mass spectrometry (HRMS) for the retrospective assessment of off-study antiretroviral drug use and the determination of potential antiretroviral therapy (ART) non-compliance.

methodsSerum standards were prepared that contained 15 antiretroviral drugs: 9 protease inhibitors (PIs), 4 nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs), and 2 non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs). Analytical separation was achieved on a Hypersil Gold PFP (100×3mm) column and the eluent was analyzed using the Thermo Exactive Orbitrap mass spectrometer (Exactive-MS) operated in full scan mode. Limit of identification, signal intensity precision, retention time analysis, selectivity, and carryover studies were conducted. Concordance with liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods was evaluated using remnant plasma samples from a clinical trial.

resultsThe limit of identification ranged from 5 to 10ng/ml for 14 drugs (9 PIs, 1 NNRTI, 4 NRTIs) and was 150ng/ml for 1 NNRTI. Precision studies with high and low control mixtures revealed signal intensity coefficients of variation of 3.0-27.5%. The Exactive-MS method was selective for the compounds of interest. Overall, concordance ranged from 89.1% to 100% for the screening of antiretroviral drugs in clinical plasma specimens as compared to LC-MS/MS methods.

conclusionUsing the Exactive-MS, we developed and validated a highly selective, robust method for the multiplexed detection of 15 antiretroviral drugs.

Indexed as

Anti-HIV AgentsBlood Chemical AnalysisHIV InfectionsHumansLimit of DetectionMass SpectrometryPatient ComplianceAnti-HIV AgentsAntiretroviralClinical trialsExactive-MSHigh-resolution mass spectrometryValidation

Identifiers

PMID24661980
PMCPMC4039613
OpenAlexW1969581657

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.