Stereospecific high-performance liquid chromatographic assay of zopiclone in human plasma

Foster, Robert T.; Caillé, Gilles; Ngoc, Anh Ho; Lemko, C.; Kherani, Raheem; Pasutto, Franco M.

doi:10.1016/0378-4347(94)00226-6

Cited by 29 publications

(19 citation statements)

References 17 publications

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“…The oxazepam samples were diluted with 0.5 ml of 0.1 M phosphate buffer, pH 5.0, followed by methanol extraction using octadecyl 3-ml solid phase extraction columns (Bakerbond; Baker BV, Deventer, The Netherlands) (Mawa et al, 1996). Zopiclone concentrations were measured using a PerkinElmer LC240 fluorescence detector (Beaconsfield, UK) at wavelengths for excitation of 300 nm and for emission of 470 nm (Foster et al, 1994).…”

Section: Methodsmentioning

confidence: 99%

Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of the Electroencephalogram Effects of GABA_AReceptor Modulators: In Vitro-in Vivo Correlations

Visser¹,

Wolters²,

Gubbens‐Stibbe³

et al. 2003

J Pharmacol Exp Ther

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A mechanism-based pharmacokinetic-pharmacodynamic (PK/ PD) model for neuroactive steroids, comprising a separate characterization of 1) the receptor activation process and 2) the stimulus-response relationship, was applied to various nonsteroidal GABA A receptor modulators. The EEG effects of nine prototypical GABA A receptor modulators (six benzodiazepines, one imidazopyridine, one cyclopyrrolone, and one ␤-carboline) were determined in rats in conjunction with plasma concentrations. Population PK/PD modeling revealed monophasic concentration-EEG effect relationships with large differences in potency (EC 50 ) and intrinsic activity between the compounds. The data were analyzed on the basis of the mechanism-based PK/PD model for (synthetic) neuroactive steroids on the assumption of a single and unique stimulus-response relationship. The model converged yielding estimates of both the apparent in vivo receptor affinity (K PD ) and the in vivo intrinsic efficacy (e PD ). The values of K PD ranged from 0.41 Ϯ 0 ng⅐ml Ϫ1 for bretazenil to 436 Ϯ 72 ng⅐ml Ϫ1 for clobazam and the values for e PD from Ϫ0.27 Ϯ 0 for methyl 6,7-dimethoxy-4-ethyl-␤-carboline-3-carboxylate to 0.54 Ϯ 0.02 for diazepam. Significant linear correlations were observed between K PD for unbound concentrations and the affinity in an in vitro receptor bioassay (r ϭ 0.93) and between e PD and the GABA-shift in vitro (r ϭ 0.95). The findings of this investigation show that the in vivo effects of nonsteroidal GABA A receptor modulators and (synthetic) neuroactive steroids can be described on the basis of a single unique transducer function. In this paradigm, the nonsteroidal GABA A receptor modulators behave as partial agonists relative to neuroactive steroids.The pharmacokinetic-pharmacodynamic correlations of benzodiazepines have been the subject of numerous studies in both animals and humans for review, see Laurijssens and Greenblatt, 1996), but the predictive value of the proposed models seems to be limited. To date, there is an increasing interest in the development of mechanism-based PK/PD models because they allow the prediction of drug effects in vivo in a strict, quantitative manner on the basis of results obtained in in vitro test systems. These models not only provide a scientific basis for the prediction of drug effects in humans on the basis of results obtained in animal studies but also allow a mechanistic understanding for observed interindividual variability in drug response (Van der Graaf and Danhof, 1997).The need for mechanism-based modeling is illustrated by the difficulty of predicting the in vivo intrinsic activity of benzodiazepine receptor partial agonists in humans on the basis of results obtained in preclinical investigations. For example, in humans, the new benzodiazepine Ro 46-2153 behaved as a full agonist, whereas it was selected from preclinical studies based on its partial agonist properties (Goggin et al., 2000).In mechanism-based PK/PD models that are based on receptor theory, a separation is made between th...

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Section: Methodsmentioning

confidence: 99%

Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of the Electroencephalogram Effects of GABA_AReceptor Modulators: In Vitro-in Vivo Correlations

Visser¹,

Wolters²,

Gubbens‐Stibbe³

et al. 2003

J Pharmacol Exp Ther

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“…Several analytical methods have been reported to detect zopiclone in biological fluids (plasma, serum, urine): capillary electrophoresis (Hempel and Blaschke, 1996), gas chromatography (Debruyne et al, 1991;Gaillard et al, 1993;Kennel et al, 1990;Stanke et al, 1996), gas chromatography-mass spectrometry (Kintz et al, 1991), liquid chromatography-mass spectrometry (Giround et al, 2003), and high-performance liquid chromatography (HPLC) with fluorescence detection Quantitation of zopiclone and desmethylzopiclone in plasma 795 ORIGINAL RESEARCH (Asberg, 1986;Fernandez et al, 1991Fernandez et al, , 1993Fernandez et al, , 2002LeLiboux et al, 1987;Miller et al, 1986;Stanley et al, 1985;Yang and Rochholz, 2002) or with ultraviolet detection (Boniface et al, 1992;Foster et al, 1994;Paw and Misztal, 2000). Several methods have been reported to detect zopiclone and its metabolite desmethylzopiclone in urine (Fernandez et al, 1993;Hempel and Blaschke, 1996;Daenens, 1994, 1996;Nordgren et al, 2002), as the metabolites are not been detected in plasma (Gaillot et al, 1983;Houghton et al, 1985;LeLiboux et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Quantitation of zopiclone and desmethylzopiclone in human plasma by high-performance liquid chromatography using fluorescence detection

Nirogi

Kandikere

Mudigonda

2006

Biomed. Chromatogr.

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A simple, reliable HPLC method using fluorescence detection (excitation 307 and emission 483 nm) was developed and validated for simultaneous quantitation of zopiclone and its metabolite desmethylzopiclone in human plasma. Following a single-step liquid-liquid extraction, the analytes and internal standard (zaleplon) were separated using an isocratic mobile phase on a reversed-phase C 18 column. The lower limit of quantitation was 3 ng/mL for zopiclone and 6 ng/mL for desmethylzopiclone with a relative standard deviation of less than 5%. A linear dynamic range of 3-300 ng/mL for zopiclone and of 6-500 ng/mL for desmethylzopiclone was established. This HPLC method was validated with between-batch precision of 1.7-4.2% and 3.2-7.5% for zopiclone and desmethylzopiclone respectively. The between-batch accuracy was 99.4-111.5% and 101.6-104.8% for zopiclone and desmethylzopiclone, respectively. Frequently coadministered drugs did not interfere with the described methodology. Stability of zopiclone and desmethylzopiclone in plasma was excellent, with no evidence of degradation during sample processing (autosampler) and 30 days' storage in a freezer. This validated method is simple and repeatable enough to be used in pharmacokinetic studies.

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“…Number of other analytical methods has been used for ZOP determination starting from potentiometric titrimetry, prescribed by British Pharmacopeia [11] through the spectrophotometry [12] up to potentiometry with ion selective electrode [13]. However, chromatographic methods including gas [14] and liquid chromatography [15][16][17], often with mass selective detection, lead the dance in the field of drug analysis.…”

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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Stereospecific high-performance liquid chromatographic assay of zopiclone in human plasma

Cited by 29 publications

References 17 publications

Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of the Electroencephalogram Effects of GABA_AReceptor Modulators: In Vitro-in Vivo Correlations

Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of the Electroencephalogram Effects of GABA_AReceptor Modulators: In Vitro-in Vivo Correlations

Quantitation of zopiclone and desmethylzopiclone in human plasma by high-performance liquid chromatography using fluorescence detection

Electrochemical oxidation of zopiclone

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Stereospecific high-performance liquid chromatographic assay of zopiclone in human plasma

Cited by 29 publications

References 17 publications

Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of the Electroencephalogram Effects of GABAAReceptor Modulators: In Vitro-in Vivo Correlations

Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of the Electroencephalogram Effects of GABAAReceptor Modulators: In Vitro-in Vivo Correlations

Quantitation of zopiclone and desmethylzopiclone in human plasma by high-performance liquid chromatography using fluorescence detection

Electrochemical oxidation of zopiclone

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Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of the Electroencephalogram Effects of GABA_AReceptor Modulators: In Vitro-in Vivo Correlations

Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling of the Electroencephalogram Effects of GABA_AReceptor Modulators: In Vitro-in Vivo Correlations