Evidence map›Paper›PMID 33713954›Full record

ArticleJournal of chromatography. B, Analytical technologies in the biomedical and life sciences2021

Development and validation of a liquid chromatography-tandem mass spectrometry method for quantifying delamanid and its metabolite in small hair samples.

Andrew Reckers, Stella Huo, Ali Esmail, Keertan Dheda, Peter Bacchetti, Monica Gandhi, John Metcalfe, Roy Gerona

Open access · greenAbstract read
In one paragraph

Article in Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.1field-weighted citation impact, top 47% 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, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
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

8 authors at 4 institutions in 2 countries.

Andrew ReckersCenter for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco (UCSF), United States.
Stella HuoDivision of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, UCSF, United States.
Ali EsmailLung Infection and Immunity Unit, Division of Pulmonology, University of Cape Town, Cape Town, South Africa.
Keertan DhedaLung Infection and Immunity Unit, Division of Pulmonology, University of Cape Town, Cape Town, South Africa.
Peter BacchettiDepartment of Epidemiology and Biostatistics, UCSF, United States.
Monica GandhiDivision of HIV, Infectious Diseases and Global Medicine, Department of Medicine, UCSF, United States.
John MetcalfeDivision of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, UCSF, United States. Electronic address: John.Metcalfe@ucsf.edu.
Roy GeronaCenter for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco (UCSF), United States. Electronic address: Roy.Gerona@ucsf.edu.
San Francisco General Hospital · USUniversity of Cape Town · ZAReproductive Science Center · USUniversity of California, San Francisco · US

Funding

Virology CoreP30AI027763 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEVEN Grant DEEKS · 1988 to 2026
$93.6M
Novel methods of pharmacologic monitoring for multidrug resistant tuberculosis treatment in the setting of HIV infectionR01AI123024 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GANDHI, MONICA, METCALFE, JOHN ZAPATA · 2016 to 2020
$3.6M
NIAID NIH HHS P30 AI027763NIAID NIH HHS R01 AI123024
6 · The paper itself

Abstract

New all-oral regimens for rifampin-resistant tuberculosis (RR-TB) are being scaled up globally. Measurement of drug concentrations in hair assesses long-term drug exposure. Delamanid (DLM) is likely to be a key component of future RR-TB treatment regimens, but a method to describe its quantification in hair via liquid chromatography-tandem mass spectrometry (LC-MS/MS) has not previously been described. We developed and validated a simple, fast, sensitive, and accurate LC-MS/MS method for quantifying DLM and its metabolite DM-6705 in small hair samples. We pulverized and extracted two milligrams of hair in methanol at 37 °C for two hours, and diluted 1:1 with water. A gradient elution method eluted DLM, DM-6705, and the internal standard OPC 14714 within 3 min, bringing overall analysis time to 5.5 min. The method has limits of detection (LOD) of 0.0003 ng/mg for DLM and 0.003 ng/mg for DM-6705. The established linear dynamic ranges are 0.003-2.1 ng/mg and 0.03-21 ng/mg for DLM and DM-6705, respectively. Eleven of 12 participant hair samples had concentrations within DLM's linear dynamic range, while all 12 samples had concentrations within the quantifiable range for DM-6705. The ranges of concentrations observed in these clinical samples for DLM and DM-6705 were 0.004-0.264 ng/mg hair and 0.412-12.041 ng/mg hair respectively. We demonstrate that while DLM was detected in hair at very low levels, its primary metabolite DM-6705 had levels approximately 100 times higher. Measuring DM-6705 in hair may accurately reflect long-term adherence to DLM-containing regimens for drug-resistant TB.

Indexed as

Chromatography, LiquidHairHumansLimit of DetectionLinear ModelsNitroimidazolesOxazolesReproducibility of ResultsTandem Mass SpectrometryTuberculosisTuberculosis, Multidrug-ResistantNitroimidazolesOPC-67683OxazolesDelamanidDM-6705Drug-resistant tuberculosisHair analysisLC-MS/MSObjective adherence metrics

Identifiers

PMID33713954
PMCPMC7987786
OpenAlexW3112791293

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.