Cited by 108Analytical Chemistry and ChromatographyAnalytical Methods in PharmaceuticalsForensic Toxicology and Drug Analysis

A parallel chiral-achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome

Open access
Moaddel, Ruin, Venkata, Swarajya Lakshmi Vattem, Tanga, Mary J., Bupp, James E., Green, Carol E., Iyer, Lalitha, Furimsky, Anna, Goldberg, Michael E. +2 more·2010·Talanta

Abstract

A parallel chiral/achiral LC-MS/MS assay has been developed and validated to measure the plasma and urine concentrations of the enantiomers of ketamine, (R)- and (S)-Ket, in complex regional pain syndrome (CRPS) patients receiving a 5-day continuous infusion of a sub-anesthetic dose of (R,S)-Ket. The method was also validated for the determination of the enantiomers of the Ket metabolites norketamine, (R)- and (S)-norKet and dehydronorketamine, (R)- and (S)-DHNK, as well as the diastereomeric metabolites hydroxynorketamine, (2S,6S)-/(2R,6R)-HNK and two hydroxyketamines, (2S,6S)-HKet and (2S,6R)-Hket. In this method, (R,S)-Ket, (R,S)-norKet and (R,S)-DHNK and the diastereomeric hydroxyl-metabolites were separated and quantified using a C(18) stationary phase and the relative enantiomeric concentrations of (R,S)-Ket, (R,S)-norKet and (R,S)-DHNK were determined using an AGP-CSP. The analysis of the results of microsomal incubations of (R)- and (S)-Ket and a plasma and urine sample from a CRPS patient indicated the presence of 10 additional compounds and glucuronides. The data from the analysis of the patient sample also demonstrated that a series of HNK metabolites were the primary metabolites in plasma and (R)- and (S)-DHNK were the major metabolites found in urine. The results suggest that norKet is the initial, but not the primary metabolite and that downstream norKet metabolites play a role in (R,S)-Ket-related pain relief in CRPS patients.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.talanta.2010.08.005

Cites

22 of 22 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Norketamine, DHNK, and (2R,6R;2S,6S)-HNK appear in human plasma as early as 40 minutes after an antidepressant ketamine dose, with (2R,6R;2S,6S)-HNK and (2S,6R;2R,6S)-HNK being the most abundant HNKs.

    “Norketamine, DHNK, and (2R,6R;2S,6S)-HNK in particular are detected in human plasma as early as 40 minutes following an antidepressant dose of ketamine (0.5 mg/kg i.v. over 40 minutes) with the most abundant HNKs being (2R,6R;2S,6S)-HNK and (2S,6R;2R,6S)-HNK”

    From Mechanisms of ketamine and its metabolites as antidepressants (2022) · cites this paper as Moaddel et al., 2010

    Results §3.4.1 reports norketamine, DHNK, and both named HNK pairs in plasma, with those HNK pairs the most abundant. But Results §3.4 and Experimental §2.7 describe sampling on day 3 of a five-day infusion for complex regional pain syndrome, not detection at 40 minutes after a 0.5 mg/kg antidepressant dose. Page numbers are unavailable in our copy. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. [3]Adams JD Jr Baillie TA Trevor AJ Castagnoli N Biomed Mass Spec 8 1981 527 538 7317567
  2. [6]Geisslinger G Hering W Thomann P Knoll R Kamp HD Br J Anaesthesia 70 1993 666 671 8329260
  3. [19]Wieber J Gugler R Hengstmann JH Dengler HJ Anaesthesist 24 1975 260 263 1155748
  4. [22]Holtman JR Crooks PA Johnson-Hardy JK Hojomat M Kleven M Wala EP Pharmacol Biochem Behavior 90 2008 676 685 18586315

Cited by

Sorted by citations

Authors
Moaddel, R., Venkata, S. L. V., Tanga, M. J., Bupp, J. E., Green, C. E., Iyer, L., Furimsky, A., Goldberg, M. E., Torjman, M. C., & Wainer, I. W.
Affiliations
  • National Institutes of Health (US)
  • SRI International (US)
  • Cooper University Hospital (US)
Corresponding author
Wainer, Irving W.
Venue
Talanta
Publisher
Elsevier BV
Published
2010-10
Volume
82
Issue
5
Pages
1892-1904
ISSN
0039-9140 (ISSN-L)
OpenAlex
W2037018768
Cited by
108
References
22
Citations by year
2026: 2 · 2025: 11 · 2024: 4 · 2023: 2 · 2022: 11 · 2021: 13 · 2020: 8 · 2019: 8 · 2018: 12 · 2017: 9 · 2016: 7 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 7
FWCI
1.76
Type
journal article
Language
en
Open access
Locations
  • Talanta (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (N01AG-3-1008)
  • National Institutes of Health
Topics
  • Physical Sciences › Chemistry › Spectroscopy › Analytical Chemistry and Chromatography
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
Keywords
ketamine, complex regional pain syndrome, stereoisomers, enantiomers, ketamine metabolites, norketamine, dehydronorketamine, hydroxynorketamine, glucuronide conjugates, microsomal metabolism, analgesia
MeSH terms
Analgesics, Biotransformation, Calibration, Chromatography, Liquid, Humans, Infusions, Intravenous, Ketamine, Reference Standards, Stereoisomerism, Reproducibility of Results, Glucuronides, Complex Regional Pain Syndromes, Tandem Mass Spectrometry

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review