Zaleplon

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Pirjo Lillsunde - One of the best experts on this subject based on the ideXlab platform.

  • fast gas chromatography negative ion chemical ionization mass spectrometry with microscale volume sample preparation for the determination of benzodiazepines and α hydroxy metabolites Zaleplon and zopiclone in whole blood
    Journal of Mass Spectrometry, 2006
    Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo Lillsunde
    Abstract:

    Fast gas chromatography/negative-ion chemical ionization mass spectrometric (GC/NICI-MS) assay combined with rapid and nonlaborious sample preparation is presented for the simultaneous determination of benzodiazepines and alpha-hydroxy metabolites, Zaleplon and zopiclone in whole blood. The compounds were extracted from 100 microl of whole blood by simultaneous multitube, microscale liquid-liquid extraction (LLE) and derivatized by N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), without the need for the time-consuming concentration stage. In the analytical separation, various parameters of fast GC/NICI-MS were applied, e.g. the use of hydrogen as a GC carrier gas, a high carrier gas velocity, a small film thickness of the analytical column, fast MS data acquisition, fast temperature ramping, and high initial and final temperatures of GC column. Sensitive identification, screening and quantitation of 18 compounds of interest were achieved in chromatographic separation in only 4.40 min. Accurate and reproducible results were obtained by using five different and carefully selected deuterated analogues on the basis of the chemical properties of the target analytes. Nevertheless, for alpha-OH-midazolam, and for bromazepam and flunitrazepam at low concentrations, the results can be considered only semiquantitative on the basis of the validation data. The extraction efficiencies ranged from 74.3 to 105.7% and the limits of quantitation (LOQ) from 1 to 100 ng ml(-1). Rapid sample preparation and fast chromatographic separation allowed cost-efficient, reliable and high sample-throughput analyses with a low amount of manual work. The method was fully validated and accredited according to EN ISO/IEC 17025 standards and is applicable for sensitive, reliable and quantitative determination of benzodiazepines, Zaleplon and zopiclone, e.g. in clinical and forensic toxicology.

  • fast gas chromatography negative ion chemical ionization mass spectrometry with microscale volume sample preparation for the determination of benzodiazepines and α hydroxy metabolites Zaleplon and zopiclone in whole blood
    Journal of Mass Spectrometry, 2006
    Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo Lillsunde
    Abstract:

    Fast gas chromatography/negative-ion chemical ionization mass spectrometric (GC/NICI-MS) assay combined with rapid and nonlaborious sample preparation is presented for the simultaneous determination of benzodiazepines and α-hydroxy metabolites, Zaleplon and zopiclone in whole blood. The compounds were extracted from 100 µl of whole blood by simultaneous multitube, microscale liquid-liquid extraction (LLE) and derivatized by N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), without the need for the time-consuming concentration stage. In the analytical separation, various parameters of fast GC/NICI-MS were applied, e.g. the use of hydrogen as a GC carrier gas, a high carrier gas velocity, a small film thickness of the analytical column, fast MS data acquisition, fast temperature ramping, and high initial and final temperatures of GC column. Sensitive identification, screening and quantitation of 18 compounds of interest were achieved in chromatographic separation in only 4.40 min. Accurate and reproducible results were obtained by using five different and carefully selected deuterated analogues on the basis of the chemical properties of the target analytes. Nevertheless, for α-OH-midazolam, and for bromazepam and flunitrazepam at low concentrations, the results can be considered only semiquantitative on the basis of the validation data. The extraction efficiencies ranged from 74.3 to 105.7% and the limits of quantitation (LOQ) from 1 to 100 ng ml−1. Rapid sample preparation and fast chromatographic separation allowed cost-efficient, reliable and high sample-throughput analyses with a low amount of manual work. The method was fully validated and accredited according to EN ISO/IEC 17025 standards and is applicable for sensitive, reliable and quantitative determination of benzodiazepines, Zaleplon and zopiclone, e.g. in clinical and forensic toxicology. Copyright © 2006 John Wiley & Sons, Ltd.

David J. Greenblatt - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacokinetic evaluation of eszopiclone: clinical and therapeutic implications.
    Expert Opinion on Drug Metabolism & Toxicology, 2012
    Co-Authors: David J. Greenblatt, Gary Zammit
    Abstract:

    Introduction: Eszopiclone is the active S-enantiomer of R,S-zopiclone, and is a cyclopyrrolone hypnotic acting via the GABA-benzodiazepine receptor system. Nearly 6 million prescriptions for eszopiclone are written yearly in the United States. Areas covered: This paper addresses the pharmacokinetic properties of eszopiclone and the extent to which the longer half-life of eszopiclone compared to other commonly used hypnotics (immediate-release zolpidem, modified-release zolpidem, triazolam, Zaleplon) may translate into either improved efficacy in enhancing sleep maintenance, or increased probability of residual sedative or performance-impairing effects. Expert opinion: Eszopiclone is metabolized mainly by Cytochrome P450-3A (CYP3A) isoforms. The mean half-life in healthy nonelderly individuals (6.1 h) is prolonged in the elderly, in patients with hepatic insufficiency, and by coadministration of CYP3A inhibitors. In clinical trials, eszopiclone consistently improves sleep maintenance relative to placebo, b...

  • pharmacokinetic profile of skp 1041 a modified release formulation of Zaleplon
    Biopharmaceutics & Drug Disposition, 2011
    Co-Authors: David J. Greenblatt, Jerold S Harmatz, James K. Walsh, Remy Luthringer, Luc Staner, Sarah Otmani, Jeanfrancois Nedelec, Celine Francart, Sarah J Parent, Corinne Staner
    Abstract:

    Objectives: Two investigations aimed to define the pharmacokinetic profile of a modified-release preparation of Zaleplon (SKP-1041). Methods. Protocol SOM001 was a 5-way crossover, double-blind, randomized trial comparing three novel modified-release formulations of Zaleplon 15 mg (SKP-1041A, SKP-1041B, SKP-1041 C) to placebo and immediate-release Zaleplon 10 mg. Protocol SOM002 was a randomized, crossover, open-label trial to compare the pharmaco- kinetics of SKP-1041B after day and night administration. In SOM001, study drug was administered at 9:00 a.m. (fasted); blood samples were obtained beginning 1 h predose through 12 h postdose. In study SOM002, study drug was administered at 9:00 a.m. or 10:30 p.m.; blood samples were obtained beginning 1 h predose through 12 h postdose. Subjects were 19 (SOM001) and 23 (SOM002) healthy adults between ages 20-46. Results. Dose-normalized total AUCs for modified-release preparations A, B, C and immediate-release Zaleplon were not significantly different; peak plasma concentrations were similar for A and B, and both were significantly higher than C. Time to peak plasma concentra- tion for A, B, and C were 4-5 h compared to 1.5 h for immediate-release Zaleplon; mean terminal phase half-life was in the range 1-2 h for A, B and immediate-release Zaleplon. No significant differences were noted between day and night administration in the SOM002 study. Conclusions. Zaleplon, 15 mg, in a novel, modified-release formulation (SKP-1041) had a time to peak plasma concentrations at 4-5 h postdose compared to 1.5 h for immediate-release Zaleplon, 10 mg. The pharmacokinetic profile suggests this formulation may be useful for treating middle-of-the-night awakening. Copyright © 2011 John Wiley & Sons, Ltd.

  • Clinically Important Drug Interactions with Zopiclone, Zolpidem and Zaleplon
    CNS Drugs, 2003
    Co-Authors: Leah M Hesse, Lisa L. Moltke, David J. Greenblatt
    Abstract:

    Insomnia, an inability to initiate or maintain sleep, affects approximately one-third of the American population. Conventional benzodiazepines, such as triazolam and midazolam, were the treatment of choice for short-term insomnia for many years but are associated with adverse effects such as rebound insomnia, withdrawal and dependency. The newer hypnosedatives include zolpidem, Zaleplon and zopiclone. These agents may be preferred over conventional benzodiazepines to treat short-term insomnia because they may be less likely to cause significant rebound insomnia or tolerance and are as efficacious as the conventional benzodiazepines. This review aims to summarise the published clinical drug interaction studies involving zolpidem, Zaleplon and zopiclone. The pharmacokinetic and pharmacodynamic interactions that may be clinically important are highlighted. Clinical trials have studied potential interactions of Zaleplon, zolpidem and zopiclone with the following types of drugs: cytochrome P450 (CYP) inducers (rifampicin), CYP inhibitors (azoles, ritonavir and erythromycin), histamine H_2 receptor antagonists (cimetidine and ranitidine), antidepressants, antipsychotics, antagonists of benzodiazepines and drugs causing sedation. Rifampicin significantly induced the metabolism of the newer hypnosedatives and decreased their sedative effects, indicating that a dose increase of these agents may be necessary when they are administered with rifampicin. Ketoconazole, erythromycin and cimetidine inhibited the metabolism of the newer hypnosedatives and enhanced their sedative effects, suggesting that a dose reduction may be required. Addition of ethanol to treatment with the newer hypnosedatives resulted in additive sedative effects without altering the pharmacokinetic parameters of the drugs. Compared with some of the conventional benzodiazepines, fewer clinically important interactions appear to have been reported in the literature with Zaleplon, zolpidem and zopiclone. The fact that these drugs are newer to the market and have not been as extensively studied as the conventional benzodiazepines may be the reason for this. Another explanation may be a difference in CYP metabolism. While triazolam and midazolam are biotransformed almost entirely via CYP3A4, the newer hypnosedatives are biotransformed by several CYP isozymes in addition to CYP3A4, resulting in CYP3A4 inhibitors and inducers having a lesser effect on their biotransformation.

  • clinically important drug interactions with zopiclone zolpidem and Zaleplon
    CNS Drugs, 2003
    Co-Authors: David J. Greenblatt, Lisa L Von Moltke, Leah M Hesse
    Abstract:

    Insomnia, an inability to initiate or maintain sleep, affects approximately one-third of the American population. Conventional benzodiazepines, such as triazolam and midazolam, were the treatment of choice for short-term insomnia for many years but are associated with adverse effects such as rebound insomnia, withdrawal and dependency. The newer hypnosedatives include zolpidem, Zaleplon and zopiclone. These agents may be preferred over conventional benzodiazepines to treat short-term insomnia because they may be less likely to cause significant rebound insomnia or tolerance and are as efficacious as the conventional benzodiazepines. This review aims to summarise the published clinical drug interaction studies involving zolpidem, Zaleplon and zopiclone. The pharmacokinetic and pharmacodynamic interactions that may be clinically important are highlighted.

  • comparative kinetics and dynamics of Zaleplon zolpidem and placebo
    Clinical Pharmacology & Therapeutics, 1998
    Co-Authors: David J. Greenblatt, Jerold S Harmatz, Lisa L Von Moltke, Bruce L Ehrenberg, L Harrel
    Abstract:

    Purpose This study evaluated the relationship of dose, plasma concentration, and time to the pharmaco-dynamics of Zaleplon and zolpidem, 2 structurally distinct benzodiazepine receptor agonists. Method Ten healthy male volunteers received single oral doses of placebo, 10 mg Zaleplon, 20 mg Zaleplon, 10 mg zolpidem, and 20 mg zolpidem in a double-blind, 5-condition crossover study, with 48 hours elapsing between trials. Plasma drug concentrations and pharmacodynamic effects were measured during the 8 to 24 hours after administration. Results Kinetics of Zaleplon and zolpidem were not significantly related to dose. However, Zaleplon had more rapid elimination (apparent elimination half-life [t½] of 1 hour) and higher apparent oral clearance (approximately 4300 mL/min) than zolpidem (t½, 2.0 to 2.2 hours; apparent oral clearance, 340 to 380 mL/min). Active treatments produced pharmacodynamic effects consistent with benzodiazepine agonist activity: self- and observer-rated sedation, impairment of digit symbol substitution test (DSST) performance, impaired memory, and increased electroencephalographic activity in the beta frequency range. The overall order of agonist potency was as follows: placebo < 10 mg Zaleplon < 20 mg Zaleplon < 10 mg zolpidem < 20 mg zolpidem; on a number of measures, 20 mg Zaleplon was comparable to 10 mg zolpidem. Quantitative effects of zolpidem 20 mg far exceeded those of other treatments. Dynamic effects of both drugs were significantly related to plasma concentration. Conclusions Benzodiazepine agonist effects of Zaleplon and zolpidem were dose and concentration dependent. At the usual clinically effective hypnotic dose (10 mg of either drug), agonist effects of zolpidem exceeded those of Zaleplon. Clinical Pharmacology & Therapeutics (1998) 64, 553–561; doi:

Teemu Gunnar - One of the best experts on this subject based on the ideXlab platform.

  • fast gas chromatography negative ion chemical ionization mass spectrometry with microscale volume sample preparation for the determination of benzodiazepines and α hydroxy metabolites Zaleplon and zopiclone in whole blood
    Journal of Mass Spectrometry, 2006
    Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo Lillsunde
    Abstract:

    Fast gas chromatography/negative-ion chemical ionization mass spectrometric (GC/NICI-MS) assay combined with rapid and nonlaborious sample preparation is presented for the simultaneous determination of benzodiazepines and alpha-hydroxy metabolites, Zaleplon and zopiclone in whole blood. The compounds were extracted from 100 microl of whole blood by simultaneous multitube, microscale liquid-liquid extraction (LLE) and derivatized by N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), without the need for the time-consuming concentration stage. In the analytical separation, various parameters of fast GC/NICI-MS were applied, e.g. the use of hydrogen as a GC carrier gas, a high carrier gas velocity, a small film thickness of the analytical column, fast MS data acquisition, fast temperature ramping, and high initial and final temperatures of GC column. Sensitive identification, screening and quantitation of 18 compounds of interest were achieved in chromatographic separation in only 4.40 min. Accurate and reproducible results were obtained by using five different and carefully selected deuterated analogues on the basis of the chemical properties of the target analytes. Nevertheless, for alpha-OH-midazolam, and for bromazepam and flunitrazepam at low concentrations, the results can be considered only semiquantitative on the basis of the validation data. The extraction efficiencies ranged from 74.3 to 105.7% and the limits of quantitation (LOQ) from 1 to 100 ng ml(-1). Rapid sample preparation and fast chromatographic separation allowed cost-efficient, reliable and high sample-throughput analyses with a low amount of manual work. The method was fully validated and accredited according to EN ISO/IEC 17025 standards and is applicable for sensitive, reliable and quantitative determination of benzodiazepines, Zaleplon and zopiclone, e.g. in clinical and forensic toxicology.

  • fast gas chromatography negative ion chemical ionization mass spectrometry with microscale volume sample preparation for the determination of benzodiazepines and α hydroxy metabolites Zaleplon and zopiclone in whole blood
    Journal of Mass Spectrometry, 2006
    Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo Lillsunde
    Abstract:

    Fast gas chromatography/negative-ion chemical ionization mass spectrometric (GC/NICI-MS) assay combined with rapid and nonlaborious sample preparation is presented for the simultaneous determination of benzodiazepines and α-hydroxy metabolites, Zaleplon and zopiclone in whole blood. The compounds were extracted from 100 µl of whole blood by simultaneous multitube, microscale liquid-liquid extraction (LLE) and derivatized by N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), without the need for the time-consuming concentration stage. In the analytical separation, various parameters of fast GC/NICI-MS were applied, e.g. the use of hydrogen as a GC carrier gas, a high carrier gas velocity, a small film thickness of the analytical column, fast MS data acquisition, fast temperature ramping, and high initial and final temperatures of GC column. Sensitive identification, screening and quantitation of 18 compounds of interest were achieved in chromatographic separation in only 4.40 min. Accurate and reproducible results were obtained by using five different and carefully selected deuterated analogues on the basis of the chemical properties of the target analytes. Nevertheless, for α-OH-midazolam, and for bromazepam and flunitrazepam at low concentrations, the results can be considered only semiquantitative on the basis of the validation data. The extraction efficiencies ranged from 74.3 to 105.7% and the limits of quantitation (LOQ) from 1 to 100 ng ml−1. Rapid sample preparation and fast chromatographic separation allowed cost-efficient, reliable and high sample-throughput analyses with a low amount of manual work. The method was fully validated and accredited according to EN ISO/IEC 17025 standards and is applicable for sensitive, reliable and quantitative determination of benzodiazepines, Zaleplon and zopiclone, e.g. in clinical and forensic toxicology. Copyright © 2006 John Wiley & Sons, Ltd.

Nerijus Karlonas - One of the best experts on this subject based on the ideXlab platform.

  • development of an spe method for the determination of Zaleplon and zopiclone in hemolyzed blood using fast gc with negative ion chemical ionization ms
    IEEE Journal of Solid-state Circuits, 2014
    Co-Authors: Nerijus Karlonas, Arunas Ramanavicius, Almira Ramanaviciene
    Abstract:

    A solid phase extraction procedure for determination of Zaleplon and zopiclone in low-volume human hemolyzed blood using fast gas chromatography with negative-ion chemical ionization mass spectrometry has been developed and validated. Both analytes were well retained on Oasis MCX and HLB columns, also sufficient extraction efficiency was achieved at pH 9.0. For further study a hydrophiliclipophilic sorbent Oasis HLB was selected due to the polarity of sorbent surface and its large surface area in order to achieve efficient extraction of both analytes in a single step. Special attention has been paid to choosing washing and eluting solvents, resulting in a particularly/extremely clean and moisture free extract. The mean extraction efficiency was higher than 90.1 % for Zaleplon, and 82.9 % for zopiclone. The precision for Zaleplon and zopiclone was between 3.04  10.58 % and 4.08  9.52 %, respectively. Whereas the accuracy was in the range from -5.73 to 6.00 %, and from -7.00 to 6.32 % for Zaleplon and zopiclone, respectively. The results have shown that the developed method is accurate, selective, precise, very fast with excellent recovery and low limits of detection and quantification.

Kari Ariniemi - One of the best experts on this subject based on the ideXlab platform.

  • fast gas chromatography negative ion chemical ionization mass spectrometry with microscale volume sample preparation for the determination of benzodiazepines and α hydroxy metabolites Zaleplon and zopiclone in whole blood
    Journal of Mass Spectrometry, 2006
    Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo Lillsunde
    Abstract:

    Fast gas chromatography/negative-ion chemical ionization mass spectrometric (GC/NICI-MS) assay combined with rapid and nonlaborious sample preparation is presented for the simultaneous determination of benzodiazepines and alpha-hydroxy metabolites, Zaleplon and zopiclone in whole blood. The compounds were extracted from 100 microl of whole blood by simultaneous multitube, microscale liquid-liquid extraction (LLE) and derivatized by N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), without the need for the time-consuming concentration stage. In the analytical separation, various parameters of fast GC/NICI-MS were applied, e.g. the use of hydrogen as a GC carrier gas, a high carrier gas velocity, a small film thickness of the analytical column, fast MS data acquisition, fast temperature ramping, and high initial and final temperatures of GC column. Sensitive identification, screening and quantitation of 18 compounds of interest were achieved in chromatographic separation in only 4.40 min. Accurate and reproducible results were obtained by using five different and carefully selected deuterated analogues on the basis of the chemical properties of the target analytes. Nevertheless, for alpha-OH-midazolam, and for bromazepam and flunitrazepam at low concentrations, the results can be considered only semiquantitative on the basis of the validation data. The extraction efficiencies ranged from 74.3 to 105.7% and the limits of quantitation (LOQ) from 1 to 100 ng ml(-1). Rapid sample preparation and fast chromatographic separation allowed cost-efficient, reliable and high sample-throughput analyses with a low amount of manual work. The method was fully validated and accredited according to EN ISO/IEC 17025 standards and is applicable for sensitive, reliable and quantitative determination of benzodiazepines, Zaleplon and zopiclone, e.g. in clinical and forensic toxicology.

  • fast gas chromatography negative ion chemical ionization mass spectrometry with microscale volume sample preparation for the determination of benzodiazepines and α hydroxy metabolites Zaleplon and zopiclone in whole blood
    Journal of Mass Spectrometry, 2006
    Co-Authors: Teemu Gunnar, Kari Ariniemi, Pirjo Lillsunde
    Abstract:

    Fast gas chromatography/negative-ion chemical ionization mass spectrometric (GC/NICI-MS) assay combined with rapid and nonlaborious sample preparation is presented for the simultaneous determination of benzodiazepines and α-hydroxy metabolites, Zaleplon and zopiclone in whole blood. The compounds were extracted from 100 µl of whole blood by simultaneous multitube, microscale liquid-liquid extraction (LLE) and derivatized by N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), without the need for the time-consuming concentration stage. In the analytical separation, various parameters of fast GC/NICI-MS were applied, e.g. the use of hydrogen as a GC carrier gas, a high carrier gas velocity, a small film thickness of the analytical column, fast MS data acquisition, fast temperature ramping, and high initial and final temperatures of GC column. Sensitive identification, screening and quantitation of 18 compounds of interest were achieved in chromatographic separation in only 4.40 min. Accurate and reproducible results were obtained by using five different and carefully selected deuterated analogues on the basis of the chemical properties of the target analytes. Nevertheless, for α-OH-midazolam, and for bromazepam and flunitrazepam at low concentrations, the results can be considered only semiquantitative on the basis of the validation data. The extraction efficiencies ranged from 74.3 to 105.7% and the limits of quantitation (LOQ) from 1 to 100 ng ml−1. Rapid sample preparation and fast chromatographic separation allowed cost-efficient, reliable and high sample-throughput analyses with a low amount of manual work. The method was fully validated and accredited according to EN ISO/IEC 17025 standards and is applicable for sensitive, reliable and quantitative determination of benzodiazepines, Zaleplon and zopiclone, e.g. in clinical and forensic toxicology. Copyright © 2006 John Wiley & Sons, Ltd.