Heart-cutting two-dimensional liquid chromatography coupled to quadrupole-orbitrap high resolution mass spectrometry for determination of N,N-dimethyltryptamine in rat plasma and brain; Method development and application.
Heart-cutting 2D-LC-HRMS/MS
N,N-dimethyltryptamine
Rat brain
Rat plasma
α-methyltryptamine
Journal
Journal of pharmaceutical and biomedical analysis
ISSN: 1873-264X
Titre abrégé: J Pharm Biomed Anal
Pays: England
ID NLM: 8309336
Informations de publication
Date de publication:
30 Nov 2020
30 Nov 2020
Historique:
received:
21
06
2020
revised:
30
08
2020
accepted:
02
09
2020
pubmed:
18
9
2020
medline:
22
6
2021
entrez:
17
9
2020
Statut:
ppublish
Résumé
The orthogonal heart-cutting liquid chromatography (LC) modes coupled to high-resolution tandem mass spectrometry (HRMS/MS) provide a number of possibilities to enhance selectivity and sensitivity for the determination of targeted compounds in complex biological matricies. Here we report the development of a new fast 2D-LC-(HRMS/MS) method and its successful application for quantitative determination of the level of plasma and brain N,N-dimethyltriptamine (DMT) using α-methyltryptamine (AMT) as internal standard in an experimental model of cerebral ischemia/reperfusion using DMT administration. The 2D-LC separation was carried out by a combination of hydrophilic interaction liquid chromatography (HILIC) in the first dimension followed by second-dimensional reversed-phase (RP) chromatography within a total run time of 10 min. The enrichment of HILIC effluent of interest containing DMT was performed using a C18 trapping column. During method development several parameters of sample preparation procedures, chromatographic separation and mass spectrometric detection were optimised to achieve high DMT recovery (plasma: 90 %, brain: 88 %) and sensitivity (plasma: 0.108 ng/mL of LOD, brain: 0.212 ng/g of LOD) applying targeted analytical method with strict LC and HRMSMS confirmatory criteria. Concerning rat plasma sample, the concentration of DMT before hypoxia (49.3-114.3 ng/mL plasma) was generally higher than that after hypoxia (10.6-96.1 ng/mL plasma). After treatment, the concentration of DMT in brain was elevated up to the range of 2-6.1 ng/g. Overall, our analytical approach is suitable to detect and confirm the presence of DMT administered to experimental animals with therapeutic purpose in a reliable manner.
Identifiants
pubmed: 32942106
pii: S0731-7085(20)31501-6
doi: 10.1016/j.jpba.2020.113615
pii:
doi:
Substances chimiques
N,N-Dimethyltryptamine
WUB601BHAA
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113615Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Authors declare no conflict of interest.