Evidence map›Paper›PMID 27454087›Full record

ArticleJournal of pharmaceutical and biomedical analysis2016

LC-MS/MS assay for the quantitation of FdCyd and its metabolites FdUrd and FU in human plasma.

Julianne L Holleran, Julie L Eiseman, Robert A Parise, Shivaani Kummar, Jan H Beumer

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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 26% 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

4 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
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 3 institutions in 1 country.

Julianne L HolleranCancer Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States.
Julie L EisemanCancer Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States; Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
Robert A PariseCancer Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States; Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, United States.
Shivaani KummarDivision of Cancer Treatment and Diagnosis, NCI, Bethesda, MD, United States.
Jan H BeumerCancer Therapeutics Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States; Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, United States; Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States. Electronic address: beumerj@gmail.com.
University of Pittsburgh · USUPMC Hillman Cancer Center · USCenter for Cancer Research · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
NCI ET-CTN with Phase i Emphasis at UPCIUM1CA186690 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD, Farshid Dayyani · 2014 to 2026
$9.1M
NCI NIH HHS HHSN261201100015CNCI NIH HHS P30 CA047904NCI NIH HHS UM1 CA186690
6 · The paper itself

Abstract

The hypomethylating agent 5-fluoro-2'-deoxycytidine (FdCyd, NSC 48006) is being evaluated clinically both via the intravenous route and via the oral route in combination with 3,4,5,6-tetrahydrouridine (THU), a potent inhibitor of FdCyd catabolism. To determine the pharmacokinetics of FdCyd and downstream metabolites, we developed and validated an LC-MS/MS assay for the quantitation of FdCyd, 5-fluoro-2'-deoxyuridine (FdUrd), and 5-fluorouracil (FU) in 0.2mL human plasma. After acetonitrile protein precipitation, the sample was split and separate chromatography was achieved for FdCyd with a Synergi Polar-RP column and for FdUrd and FU with a Shodex Asahipak NH2P-50 2D column. Gradients of 0.1% acetic acid in acetonitrile and water were used. Detection with a Quattromicro quadrupole mass spectrometer with electrospray ionization in positive-ion (FdCyd) or negative-ion (FdUrd and FU) multiple reaction monitoring (MRM) mode. The assay was linear from 5 to 3000ng/mL for all three analytes and proved to be accurate (96.7-105.5%) and precise (<8.1%CV), and fulfilled FDA criteria for bioanalytical method validation. We demonstrated the suitability of this assay for measuring FdCyd and metabolites FdUrd and FU in plasma from a patient who was administered 120mg PO FdCyd 30min after 3000mg THU. Our LC-MS/MS assay will be an essential tool to further define the pharmacology of FdCyd in ongoing and future studies.

Indexed as

Biological AssayChromatography, LiquidDeoxyuridineFluorouracilHumansPlasmaTandem Mass SpectrometryTetrahydrouridine5-fluoro-2'-deoxyuridineDeoxyuridineFluorouracilTetrahydrouridineAssayFdCydMetabolitesTandem mass spectrometryValidation

Identifiers

PMID27454087
PMCPMC5003709
OpenAlexW2484326582

What OpenQuestion holds

Textmetadata
LicenceTDM
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.