Evidence map›Paper›PMID 21715120›Full record

ArticleJournal of pharmaceutical and biomedical analysis2011

Determination of nucleoside analog mono-, di-, and tri-phosphates in cellular matrix by solid phase extraction and ultra-sensitive LC-MS/MS detection.

Lane R Bushman, Jennifer J Kiser, Joseph E Rower, Brandon Klein, Jia-Hua Zheng, Michelle L Ray, Peter L Anderson

2 registry-linked trialsAbstract readValidation Study
In one paragraph

Article in Journal of pharmaceutical and biomedical analysis, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 77 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 6% 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.

NCT02588287 nacompletednot on this mapstarted 2015, after this paper: background citation

Effects of Sofosbuvir/Ledipasvir Treatment on the Pharmacokinetics and Renal Safety of Tenofovir

TypeinterventionalSponsorUniversity of Colorado, DenverRan2015 to 2016Enrolled14ConditionsHepatitis C and HIV CoinfectionArmsBlood draws for tenofovir PK, renal function
NCT03126370 phase4completednot on this mapstarted 2018, after this paper: background citation

Effects of Ledipasvir/Sofosbuvir Treatment on the Pharmacokinetics and Renal Safety of Tenofovir Alafenamide (TAF) in Patients With HIV.

TypeinterventionalSponsorUniversity of Colorado, DenverRan2018 to 2019Enrolled10ConditionsHepatitis C, HIV CoinfectionArmsTDF with a boosted protease inhibitor, TAF with a boosted protease inhibitor, TAF with a boosted protease inhibitor and LDV/SOF
3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.

  1. Pooled it
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  3. A Real-Time Urine Tenofovir Assay Improves Drug Adherence Among People With HIV With Prior Virologic Failure in a Randomized Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
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  13. Characterization of HIV Seroconverters in a TDF/FTC PrEP Study: HPTN 067/ADAPT.Journal of acquired immune deficiency syndromes (1999) · 2017
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17 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Lane R BushmanDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Mail Stop V20-C238, 12850 E. Montview Blvd., Aurora, Colorado 80045, USA.
Jennifer J Kiser
Joseph E Rower
Brandon Klein
Jia-Hua Zheng
Michelle L Ray
Peter L Anderson
University of Colorado Denver · US

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025780 · NCRR · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2008 to 2011
$61.3M
Cellular pharmacology of tenofovir and emtricitabine for HIV prophylaxisU01AI084735 · NIAID · UNIVERSITY OF COLORADO DENVER · PI ANDERSON, PETER L. · 2009 to 2012
$4.2M
Sex and disease dependent nucleoside analog toxicityR01AI064029 · NIAID · UNIVERSITY OF COLORADO DENVER · PI ANDERSON, PETER L. · 2005 to 2009
$1.7M
UPLC-MS for pharmacology studies in HIVS10RR023442 · NCRR · UNIVERSITY OF COLORADO DENVER · PI ANDERSON, PETER L. · 2008 to 2008
$400k
NCRR NIH HHS 1UL1 RR025780NCRR NIH HHS S10 RR023442NCRR NIH HHS S10 RR23442NCRR NIH HHS UL1 RR025780NIAID NIH HHS R01 AI064029NIAID NIH HHS R01 AI64029NIAID NIH HHS U01 AI084735NIAID NIH HHS U01 AI84735NIDDK NIH HHS K23 DK82321
6 · The paper itself

Abstract

An ultra-sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) assay was developed and validated to facilitate the assessment of clinical pharmacokinetics of nucleotide analogs from lysed intracellular matrix. The method utilized a strong anion exchange isolation of mono-(MP), di-(DP), and tri-phosphates (TP) from intracellular matrix. Each fraction was then dephosphorylated to the parent moiety yielding a molar equivalent to the original nucleotide analog intracellular concentration. The analytical portion of the methodology was optimized in specific nucleoside analog centric modes (i.e. tenofovir (TFV) centric, zidovudine (ZDV) centric), which included desalting/concentration by solid phase extraction and detection by LC-MS/MS. Nucleotide analog MP-, DP-, and TP-determined on the TFV centric mode of analysis include TFV, lamivudine (3TC), and emtricitibine (FTC). The quantifiable linear range for TFV was 2.5-2000 fmol/sample, and that for 3TC/FTC was 0.1 200 pmol/sample. Nucleoside analog MP-, DP-, and TP-determined on the ZDV centric mode of analysis included 3TC and ZDV. The quantifiable linear range for 3TC was 0.1 100 pmol/sample, and 5-2000 fmol/sample for ZDV. Stable labeled isotopic internal standards facilitated accuracy and precision in alternative cell matrices, which supported the intended use of the method for MP, DP, and TP determinations in various cell types. The method was successfully applied to clinical research samples generating novel intracellular information for TFV, FTC, ZDV, and 3TC nucleotides. This document outlines method development, validation, and application to clinical research.

Indexed as

Chromatography, LiquidSolid Phase ExtractionTandem Mass SpectrometryAdenineAnion Exchange ResinsAntiviral AgentsCalibrationDeoxycytidineDiphosphatesEmtricitabineHumansLamivudineLeukocytes, MononuclearNucleosidesOrganophosphonatesPhosphatesAdenineAnion Exchange ResinsAntiviral AgentsDeoxycytidineDiphosphatesEmtricitabineLamivudineNucleosidesOrganophosphonatesPhosphatesTenofovirZidovudine

Identifiers

PMID21715120
PMCPMC3153375
OpenAlexW1984521402

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.