Structural elucidation of amino amide-type local anesthetic drugs and their main metabolites in urine by LC-MS after derivatization and its application for differentiation between positional isomers of prilocaine.
LC-ESI-MS/MS
carbamylation
derivatization
local anesthetic drugs
oxidation
prilocaine isomers
Journal
Journal of mass spectrometry : JMS
ISSN: 1096-9888
Titre abrégé: J Mass Spectrom
Pays: England
ID NLM: 9504818
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
15
06
2020
revised:
24
08
2020
accepted:
28
08
2020
entrez:
24
9
2020
pubmed:
25
9
2020
medline:
20
8
2021
Statut:
ppublish
Résumé
The demand for clinical toxicology analytical methods for identifying drugs of abuse and medicinal drugs is steadily increasing. Structural elucidation of amino amide-type local anesthetic drugs and their main metabolites by GC-EI-MS and LC-ESI-MS/MS is of great analytical challenge. These compounds exhibit only/mostly fragments/product ions representing the amine-containing residue, while the aromatic amide moiety remains unidentified. This task becomes even more complicated when discrimination between positional isomers of such compounds is required. Here, we report the development of a derivatization procedure for the differentiation and structural elucidation of a mixture of local anesthetic drugs and their metabolites that possess tertiary and secondary amines in water and urine. A method based on two sequential "in-vial" instantaneous derivatization processes at ambient temperature followed by LC-ESI-MS/MS analysis was developed. 2,2,2-Trichloro-1,1-dimethylethyl chloroformate (TCDMECF) was utilized to selectively convert the secondary amines into their carbamate derivatives, followed by hydrogen peroxide addition to produce the corresponding tertiary amine oxides. The resulting derivatives exhibited rich fragmentation patterns, enabling improved structural elucidation of the original compounds. The developed method was successfully applied to the differentiation and structural elucidation of prilocaine and its four positional isomers, which all possess similar GC and LC retention times and four of them exhibit almost identical EI-MS and ESI-MS/MS spectra, enabling their structural elucidation in a single LC-ESI-MS/MS analysis. The developed technique is fast and simple and enables discrimination between isomers based on different diagnostic ions/fragmentation patterns.
Substances chimiques
Amides
0
Anesthetics, Local
0
Prilocaine
046O35D44R
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e4654Informations de copyright
© 2020 John Wiley & Sons, Ltd.
Références
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