Evidence map›Paper›PMID 29433097›Full record

ArticleJournal of pharmaceutical and biomedical analysis2018

Validation and implementation of liquid chromatographic-mass spectrometric (LC-MS) methods for the quantification of tenofovir prodrugs.

Pamela Hummert, Teresa L Parsons, Laura M Ensign, Thuy Hoang, Mark A Marzinke

Abstract read
In one paragraph

Article in Journal of pharmaceutical and biomedical analysis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

17 citing papers in PubMed, 26 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

5 authors at 2 institutions in 1 country.

Pamela HummertDepartment of Medicine, Baltimore, MD, 21287, USA; Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Mason F. Lord Center Tower, Baltimore, MD, 21224, USA.
Teresa L ParsonsDepartment of Medicine, Baltimore, MD, 21287, USA; Johns Hopkins University School of Medicine, 4940 Eastern Avenue, Mason F. Lord Center Tower, Baltimore, MD, 21224, USA.
Laura M EnsignDepartment of Opthamology, Baltimore, MD, 21287, USA.
Thuy HoangDepartment of Pharmacology and Molecular Sciences, Baltimore, MD, 21287, USA.
Mark A MarzinkeDepartment of Medicine, Baltimore, MD, 21287, USA; Department of Pathology, Baltimore, MD, 21287, USA; Johns Hopkins University School of Medicine, 1800 Orleans Street, Sheikh Zayed Tower, B1020-G, Baltimore, MD, 21287, USA. Electronic address: mmarzin1@jhmi.edu.
Johns Hopkins University · USJohns Hopkins Medicine · US

Funding

Tissue pharmacology imaging and modelingU19AI113127 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BUMPUS, NAMANDJE N · 2014 to 2018
$20.7M
NIAID NIH HHS U19 AI113127
6 · The paper itself

Abstract

backgroundThe nucleotide reverse transcriptase inhibitor tenofovir (TFV) is widely administered in a disoproxil prodrug form (tenofovir disoproxil fumarate, TDF) for HIV management and prevention. Recently, novel prodrugs tenofovir alafenamide fumarate (TAF) and hexadecyloxypropyl tenofovir (CMX157) have been pursued for HIV treatment while minimizing adverse effects associated with systemic TFV exposure. Dynamic and sensitive bioanalytical tools are required to characterize the pharmacokinetics of these prodrugs in systemic circulation. Two parallel methods have been developed, one to combinatorially quantify TAF and TFV, and a second method for CMX157 quantification, in plasma.

methodsK

resultsAnalytical methods: were optimized for the multiplexed monitoring of TAF and TFV, and CMX157 in plasma. The lower limits of quantification (LLOQs) for TAF, TFV, and CMX157 were 0.03, 1.0, and 0.25 ng/mL, respectively. Calibration curves were generated via weighted linear regression of standards. Intra- and inter-assay precision and accuracy studies demonstrated %CVs ≤ 14.4% and %DEVs ≤ ± 7.95%, respectively. Stability and matrix effects studies were also performed. All results were acceptable and in accordance with the recommended guidelines for bioanalytical methods. Assays were also applied to quantify in vivo concentrations of prodrugs and TFV in a preclinical study post-rectal administration.

conclusionsSensitive, specific, and dynamic LC-MS/MS assays have been developed and validated for the multiplexed quantification TAF and TFV, as well as an independent assay for CMX157 quantification, in plasma. The described methods meet sufficient throughput criteria to support large research trials.

Indexed as

AdenineAlanineAnti-HIV AgentsChromatography, LiquidHumansOrganophosphonatesProdrugsTandem Mass SpectrometryTenofovirAdenineAlanineAnti-HIV Agentshexadecyloxypropyl 9-(2-(phosphonomethoxy)propyl)adenineOrganophosphonatesProdrugsTenofovirtenofovir alafenamideAntiretroviralHIVLC–MS/MSProdrugTenofovirValidation

Identifiers

PMID29433097
PMCPMC5835418
OpenAlexW2789526849

What OpenQuestion holds

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Read underepoch 390

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.