Enantioselective analysis of zopiclone in rat brain by liquid chromatography tandem mass spectrometry

Tonon, Milena Araújo; Jabor, Valquíria Aparecida Polisel; Bonato, Pierina Sueli

doi:10.1007/s00216-012-6487-4

Cited by 6 publications

(7 citation statements)

References 15 publications

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“…A new LC method with triple quadrupole mass spectrometry detection was developed and validated for the quantification of zopiclone enantiomers using SPE as sample preparation technique in rat brain. Zopiclone enantiomers were resolved on a Chiralpak AD column with a mobile phase consisting of acetonitrile/ethanol/methanol (Tonon et al, 2013).…”

Section: Nonamphetamine Cns Stimulantsmentioning

confidence: 99%

Stereo‐specific LC and LC‐MS bioassays of antidepressants and psychotics

Rao

Prasad

2014

Biomedical Chromatography

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Stereochemistry in drug action is gaining importance because the enantiomers often differ in their biological activity and pharmacokinetic profiles. The use of racemic drugs may contribute to adverse effects owing to the presence of either inactive or toxic enantiomers. Most of the drugs currently used to treat psychiatric disorders, including depression, contain one or more chiral centers and are mostly sold as racemates. Single-enantiomer drugs provide greater selectivity for their biological targets, improved therapeutic indices and better pharmacokinetics compared with racemates. Therefore it is of great importance to monitor body fluid/tissue levels of drugs used to treat depression and psychiatric disorders. The present manuscript gives an overview of liquid chromatographic and mass spectrometric techniques reported during 2000-2013 for enantiomeric separation of various classes of antidepressants, viz. selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, noradrenergic and specific serotonergic antidepressants, norepinephrine reuptake inhibitors, norepinephrine-dopamine reuptake inhibitors, nonamphetamine central nervous system stimulants, serotonin and dopamine inhibitors and γ-aminobutyric acid receptor agonists in biological matrices. Techniques used for extraction, separation and quantification are discussed.

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Section: Nonamphetamine Cns Stimulantsmentioning

confidence: 99%

Stereo‐specific LC and LC‐MS bioassays of antidepressants and psychotics

Rao

Prasad

2014

Biomedical Chromatography

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“…Among them, chiral analysis of ZOP is particularly important for forensic scientists because each enantiomer might be under different legal restrictions. Many previous studies have used liquid–liquid extraction or solid‐phase extraction (SPE) combined with capillary electrophoresis [4] or liquid chromatography (LC) [6–9]. In these chiral analyses, ZOP was separated using chiral additives [4] or chiral stationary phases [6–9], which are enantioselective and interact with each enantiomer differently.…”

Section: Introductionmentioning

confidence: 99%

“…To date, both chiral [4][5][6][7][8][9] and achiral [10][11][12] analyses of ZOP in biological specimens have been reported. Among them, chiral analysis of ZOP is particularly important for forensic scientists because each enantiomer might be under different legal restrictions.…”

mentioning

confidence: 99%

“…Many previous studies have used liquid-liquid extraction or solidphase extraction (SPE) combined with capillary electrophoresis [4] or liquid chromatography (LC) [6][7][8][9]. In these chiral analyses, ZOP was separated using chiral additives [4] or chiral stationary phases [6][7][8][9], which are enantioselective and interact with each enantiomer differently. Chiral separation of ZOP was achieved by this enantioselective interaction.…”

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confidence: 99%

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Rapid enantiomeric analysis of zopiclone in serum by supercritical fluid chromatography–tandem mass spectrometry

Segawa

Iwata

Okada

et al. 2023

Journal of Forensic Sciences

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Zopiclone (ZOP) is a hypnotic drug prescribed to treat insomnia. Due to the chiral nature of ZOP, the psychologically active S‐form and inactive R‐form need to be determined enantiomerically in a forensic drug analysis. In the present study, a supercritical fluid chromatography (SFC) method was designed with a faster analysis ability than that of previously reported techniques. The SFC–tandem mass spectrometry (SFC–MS/MS) method was optimized using a column with a chiral polysaccharide stationary phase (Trefoil CEL2). ZOP was extracted from pooled human serum using solid‐phase extraction (Oasis HLB) and analyzed. The developed SFC–MS/MS method achieved the baseline separation of S‐ZOP and R‐ZOP within 2 min. The fit‐for‐purpose method validation indicated that the optimized solid‐phase extraction achieved near complete recovery and approximately 70% of the matrix effect. Both the retention time and peak area showed sufficient precision. The lower and upper limits of quantification (LOQ) were 5.7 × 10−2 ng/mL and 25 ng/mL for R‐ZOP, and 5.2 × 10−2 ng/mL and 25 ng/mL for S‐ZOP. The calibration line was linear in the range from lower LOQ to upper LOQ. The stability test indicated that ZOP in serum stored in a refrigerator (4°C) degraded and about 55% remained in 31 days. The quick analysis of the SFC–MS/MS method makes it a valid option for the enantiomeric analysis of ZOP.

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“…Both enantiomers are metabolised via cytochrome P450 enzyme system [1]. The main biotransformation products of oxidative metabolism are N-desmethyl zopiclone and zopiclone N-oxide [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Electrochemical oxidation of zopiclone

et al. 2015

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Electrochemical behaviour of zopiclone was investigated on glassy carbon electrode in static and rotation disc arrangement. Strong influence of kinetics and adsorption phenomena on the electrode processes was proved by voltammetric techniques. Controlled potential electrolysis in off-line and on-line combination with tandem mass spectrometry was employed for investigation of the products of electrochemical oxidation. N-Desmethyl zopiclone was identified and three other oxidation products formed by an introduction of one or two oxygen atom(s) to the molecule of zopiclone (including zopiclone N-oxide) were characterized. Based on mass spectrometric investigation of those products, piperazine moiety was proved as a target of electrochemical oxidation of zopiclone. Since Ndesmethyl zopiclone and zopiclone N-oxide have been reported as products of enzymatic metabolism of the drug, the combination of electrochemistry with mass spectrometry may be considered as a reliable tool for simulation of some metabolic transformations. Graphical abstract

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Enantioselective analysis of zopiclone in rat brain by liquid chromatography tandem mass spectrometry

Cited by 6 publications

References 15 publications

Stereo‐specific LC and LC‐MS bioassays of antidepressants and psychotics

Stereo‐specific LC and LC‐MS bioassays of antidepressants and psychotics

Rapid enantiomeric analysis of zopiclone in serum by supercritical fluid chromatography–tandem mass spectrometry

Electrochemical oxidation of zopiclone

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