Determination of zaleplon and zolpidem by liquid chromatography–turbo-ionspray mass spectrometry: application to forensic cases

Giroud, Christian; Augsburger, Marc; Ménétrey, Annick; Mangin, Patrice

doi:10.1016/s1570-0232(03)00135-1

Cited by 34 publications

(32 citation statements)

References 15 publications

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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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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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“…The innovation described herein adapts these same methods to measurements of filter-retained, membrane bound compound in addition to the measurements of tissue homogenates. In the context of forensic analysis, a host of LC/MS/MS methods have been published in order to detect zolpidem and zopiclone in human biomatrices such as whole blood [24], plasma [25], saliva [26][27][28], urine [29] and hair [29][30][31]. Methods for concentration determinations of the two zopiclone enantiomers in human plasma have also been developed to examine stereoselective human metabolism [32][33], differential benzodiazepine receptor binding [20] and solution/plasma racemization [35].…”

Section: Lc/ms/ms Methodologymentioning

confidence: 99%

In vivo saturation binding of GABA‐A receptor ligands to estimate receptor occupancy using liquid chromatography/tandem mass spectrometry

Hopkins

Nofsinger

Allen

et al. 2009

Biopharm & Drug Disp

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Typically, the dose-occupancy curves for GABA-A receptor ligands are determined using in vivo binding of [3H]flumazenil. This study describes in vivo binding experiments without the use of tracer ligands. Bound and free fractions were measured directly using a highly sensitive LC/MS/MS detection method after in vivo administration of the GABA-A ligands zolpidem, (RS)-zopiclone, L-838417 and flumazenil, to demonstrate affinity and saturation of the filter-retained, membrane-bound fraction. The in vivo binding of flumazenil and L-838417 both saturated around 200 nM, at a similar level to the specific binding of (S)-zopiclone after doses of the racemic zopiclone, using (R)-zopiclone to estimate non-specific binding. This saturable component represented an estimate of benzodiazepine binding sites available on GABA-A receptors in vivo (200 nM). Dose-occupancy curves were constructed to estimate the dose required to achieve 50% occupancy and matched estimates obtained with tracer methods. In contrast to tracer methods, this method is uniquely suitable to the demonstration of stereoselective binding of the (S)-isomer in vivo after doses of racemic zopiclone. These results demonstrate that the LC/MS/MS measurements of total drug concentrations typically used in early drug development can be adapted to provide information about receptor occupancy in vivo.

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“…Since they are often related to drug-facilitated crimes, they have been more frequently analyzed in biological materials [3][4][5][6][7][8]. In the literature, several methods for the determination of zolpidem in biologi-cal samples including liquid chromatography with fluorescence [9][10][11][12], ultraviolet [13,14] or mass detection [15][16][17][18], gas chromatography [19][20][21][22], and capillary electrophoresis [23] can be found. Further, separation and analysis of zolpidem and its synthetic intermediates and potential synthetic impurities were conducted by gradient HPLC method [24].…”

Section: Introductionmentioning

confidence: 99%

Stress degradation studies on zolpidem tartrate using LC-DAD and LC-MS methods

Malesevic

Živanović²,

Protić³

et al. 2014

Acta Chromatographica

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Summary. The present study was designed to characterize the possible degradation products of zolpidem tartrate under various stress conditions according to International Conference on Harmonization (ICH) guidelines Q1A(R2). After exposure to light, heat, hydrolysis, and oxidation, the drug significantly degraded under photolytic and acid/base hydrolytic conditions. Degradation resulted in the formation of four key degradants. Degradation products were resolved from each other and the drug by employing an isocratic elution method on Luna C 18 column with mobile phase consisting of methanol-10 mM ammonium acetate (68.4:31.6, v/v), wherein pH was adjusted to 5.4 with glacial acetic acid. To characterize the degradation products, a method was extended to LC-MS and a mass fragmentation pattern was established using single quadrupole. The degradants were identified as zolpacid, oxozolpidem, zolpaldehyde, and zolpyridine. Finally, the most possible degradation mechanism of zolpidem tartrate in different environments was proposed.

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Determination of zaleplon and zolpidem by liquid chromatography–turbo-ionspray mass spectrometry: application to forensic cases

Cited by 34 publications

References 15 publications

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

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

In vivo saturation binding of GABA‐A receptor ligands to estimate receptor occupancy using liquid chromatography/tandem mass spectrometry

Stress degradation studies on zolpidem tartrate using LC-DAD and LC-MS methods

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