Evidence map›Paper›PMID 26678179›Full record

ArticleJournal of pharmaceutical and biomedical analysis2016

A sensitive high performance liquid chromatography assay for the quantification of doxorubicin associated with DNA in tumor and tissues.

Andrew T Lucas, Sara K O'Neal, Charlene M Santos, Taylor F White, William C Zamboni

Abstract read
In one paragraph

Article in Journal of pharmaceutical and biomedical analysis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.3field-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

12 citing papers in PubMed, 40 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 1 institution in 1 country.

Andrew T LucasDivision of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill (UNC) Eshelman School of Pharmacy, CB# 7569, Chapel Hill, NC 27599-7569, United States. Electronic address: andrew_lucas@unc.edu.
Sara K O'NealDivision of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill (UNC) Eshelman School of Pharmacy, CB# 7569, Chapel Hill, NC 27599-7569, United States. Electronic address: sarakoneal@gmail.com.
Charlene M SantosUNC Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, CB# 7295, Chapel Hill, NC 27599-7295, United States; LCCC Animal Studies Core Facility, University of North Carolina at Chapel Hill, 1002 Mary Ellen Jones Building, Chapel Hill, NC 27599-7295, United States. Electronic address: smross@email.unc.edu.
Taylor F WhiteUNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, CB#7355, Chapel Hill, NC 27599-7355, United States. Electronic address: tfwhite86@gmail.com.
William C ZamboniDivision of Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill (UNC) Eshelman School of Pharmacy, CB# 7569, Chapel Hill, NC 27599-7569, United States; UNC Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, CB# 7295, Chapel Hill, NC 27599-7295, United States; UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, CB#7355, Chapel Hill, NC 27599-7355, United States; UNC Center for Pharmacogenomics and Individualized Therapy, 120 Mason Farm Road, CB# 7361, Chapel Hill, NC 27599, United States; Carolina Institute For NanoMedicine, University of North Carolina at Chapel Hill, 120 Mason Farm Road, 1079 Genetic Medicine Building, Chapel Hill, NC 27599-7264, United States. Electronic address: zamboni@email.unc.edu.
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Re-Entry Supplement: Investigation of Oral Microbial Enzymes for the Detection and Treatment of Periodontal DiseaseUL1TR002489 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, SHAHEEN, NICHOLAS J · 2018 to 2022
$48.6M
UNC CLINICAL AND TRANSLATIONAL SCIENCE AWARD: BPCAUL1RR025747 · NCRR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RUNGE, MARSCHALL S. · 2008 to 2011
$44.6M
North Carolina Translational & Clinical Sciences Institute (NC TraCS)UL1TR001111 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BUSE, JOHN BERNARD, CAREY, TIMOTHY S · 2013 to 2017
$43.9M
Translational Nanosystems for Improved Lung Cancer Treatment with Small MoleculesU54CA151652 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DESIMONE, JOSEPH M. · 2010 to 2014
$12.1M
NCATS NIH HHS UL1 TR001111NCATS NIH HHS UL1 TR002489NCI NIH HHS CA16086NCI NIH HHS P30 CA016086NCI NIH HHS U54 CA151652NCI NIH HHS U54CA151652NCRR NIH HHS UL1 RR025747NCRR NIH HHS UL1RR025747
6 · The paper itself

Abstract

Doxorubicin, a widely used anticancer agent, exhibits antitumor activity against a wide variety of malignancies. The drug exerts its cytotoxic effects by binding to and intercalating within the DNA of tumor and tissue cells. However, current assays are unable to accurately determine the concentration of the intracellular active form of doxorubicin. Thus, the development of a sample processing method and a high-performance liquid chromatography (HPLC) methodology was performed in order to quantify doxorubicin that is associated with DNA in tumors and tissues, which provided an intracellular cytotoxic measure of doxorubicin exposure after administration of small molecule and nanoparticle formulations of doxorubicin. The assay uses daunorubicin as an internal standard; liquid-liquid phase extraction to isolate drug associated with DNA; a Shimadzu HPLC with fluorescence detection equipped with a Phenomenex Luna C18 (2μm, 2.0×100mm) analytical column and a gradient mobile phase of 0.1% formic acid in water or acetonitrile for separation and quantification. The assay has a lower limit of detection (LLOQ) of 10ng/mL and is shown to be linear up to 3000ng/mL. The intra- and inter-day precision of the assay expressed as a coefficient of variation (CV%) ranged from 4.01 to 8.81%. Furthermore, the suitability of this assay for measuring doxorubicin associated with DNA in vivo was demonstrated by using it to quantify the doxorubicin concentration within tumor samples from SKOV3 and HEC1A mice obtained 72h after administration of PEGylated liposomal doxorubicin (Doxil(®); PLD) at 6mg/kg IV x 1. This HPLC assay allows for sensitive intracellular quantification of doxorubicin and will be an important tool for future studies evaluating intracellular pharmacokinetics of doxorubicin and various nanoparticle formulations of doxorubicin.

Indexed as

AnimalsAntibiotics, AntineoplasticCell Line, TumorChromatography, High Pressure LiquidDNADNA AdductsDoxorubicinDrug StabilityFemaleHumansLimit of DetectionLiverMice, SCIDOvarian NeoplasmsReproducibility of ResultsTissue DistributionAntibiotics, Antineoplasticcalf thymus DNADNADNA AdductsDoxorubicindoxorubicin-DNADoxorubicinHPLCIntracellular doxorubicinIntracellular pharmacokineticsPEGylated liposomal doxorubicin

Identifiers

PMID26678179
PMCPMC4703077
OpenAlexW2173383263

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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.