Remimazolam, which is designed to undergo rapid hydrolysis in the body by nonspecific tissue esterases to its pharmacologically inactive carboxylic acid metabolite (M1), is a new chemical entity
been demonstrated reproductive toxicity and teratogenic potential in Wistar rats [ 12 ].
Literature about quinocetone metabolites have been reported in animals, such as rats, pigs, broilers, chickens, and carp [ 13–17 ]. Also, 3
-MS/MS [ 16 ]. Another method, UPLC-MS/MS, has high sensitivity and good selectivity. So far, there have been several reports on the detection of carbofuran and its metabolite, 3-hydroxycarbofuran in vivo or in vitro [ 10, 17–20 ]. However, to our best
yet. It was found that the main metabolite is O -desmethyl lacosamide with no anticonvulsant activity. Other metabolites, especially from polar fraction, have not been characterized so far [ 25 , 26 ].
The main goal of this study was to
A series of new (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography—tandem mass spectrometry (UHPLC—MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (LOQ) was 1.3 ng mL−1 for DE-EDCP and 0.3 μg mL−1 for EDCP. The calibration curves were linear over the concentration range of 1.3–26.7 ng mL−1 and 0.3–6.7 μg mL−1 for DE-EDCP and EDCP, respectively. Precision (%CV) and accuracy (%RE) for DE-EDCP and EDCP ranged from 3.5% to 16.0% and from 1.8% to 14.4%, respectively.
The validation process was performed in accordance with the regulatory guidance/guideline, and all of the obtained results met the established acceptance criteria. The newly developed and validated UHPLC—MS/MS method is rapid, sensitive, and selective, and it can be successfully applied to drug monitoring in nonclinical studies.
metabolite of MCPT in rat plasma and tissues via high-performance liquid chromatography (HPLC)/photodiode array detection (PDA) and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) analysis. Meanwhile, we established a validated
its metabolite carbamazepine-10,11-epoxide (CBZ-epoxide), phenytoin (PHT), valproic acid (VPA), to identify an individual reference concentration and improve treatment safety and efficacy [ 3 ]. In addition, TDMs of second‐generation AEDs were defined