Methods For The Analysis of Nonbenzodiazepine Hypnotic Drugs in Biological Matrices

Tonon, Milena Araújo; Bonato, Pierina Sueli

doi:10.4155/bio.11.313

Cited by 8 publications

(9 citation statements)

References 79 publications

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“…The principal mode of analysis remains gas or liquid chromatography with the detection method of choice being mass spectrometry, due to its rapid turnaround time and low limits of quantification [46]. These techniques are also useful in screening for CNS depressants, including benzodiazepines and Z-drugs, such as in cases of unknown drug exposure.…”

Section: Analysis and Detection Of Z-drugsmentioning

confidence: 99%

“…Comparative toxicity between the Z-drugs has been difficult to quantify due to the fact that the denominator is unknown. However, for zaleplon, the improved References include [46][47][48][49][50][51][52] ESI electrospray ionization, GC gas chromatography, HPLC high-performance liquid chromatography, LC liquid chromatography, LIF laserinduced fluorescence, LLE liquid-liquid extraction, MS mass spectroscopy, SPE solid-phase extraction, UV ultraviolet, PM postmortem, PMR postmortem redistribution Therapeutic maximal concentrations are in plasma and shown with corresponding administered doses (in parentheses). Postmortem levels are in whole blood; blood/plasma ratio for zopiclone and zaleplon is 1.…”

Section: Clinical Toxicology Of Z-drugsmentioning

confidence: 99%

“…With increasing frequency of Z-drug prescriptions and abuse in Europe and North America, benzodiazepine screening tests that employ highly sensitive mass spectrometers are recommended to routinely include Z-drugs. Techniques used in the analysis and detection of Z-drugs in various biological matrices are shown in Table 3 [46][47][48][49][50][51][52].…”

Section: Analysis and Detection Of Z-drugsmentioning

confidence: 99%

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The Clinical and Forensic Toxicology of Z-drugs

Gunja

2013

J. Med. Toxicol.

164

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The Z-drugs zolpidem, zopiclone, and zaleplon were hailed as the innovative hypnotics of the new millennium, an improvement to traditional benzodiazepines in the management of insomnia. Increasing reports of adverse events including bizarre behavior and falls in the elderly have prompted calls for caution and regulation. Z-drugs have significant hypnotic effects by reducing sleep latency and improving sleep quality, though duration of sleep may not be significantly increased. Z-drugs exert their effects through increased γ-aminobutyric acid (GABA) transmission at the same GABA-type A receptor as benzodiazepines. Their pharmacokinetics approach those of the ideal hypnotic with rapid onset within 30 min and short half-life (1-7 h). Zopiclone with the longest duration of action has the greatest residual effect, similar to short-acting benzodiazepines. Neuropsychiatric adverse events have been reported with zolpidem including hallucinations, amnesia, and parasomnia. Poisoning with Z-drugs involves predominantly sedation and coma with supportive management being adequate in the majority. Flumazenil has been reported to reverse sedation from all three Z-drugs. Deaths from Z-drugs are rare and more likely to occur with polydrug overdose. Zdrugs can be detected in blood, urine, oral fluid, and postmortem specimens, predominantly with liquid chromatography-mass spectrometry techniques. Zolpidem and zaleplon exhibit significant postmortem redistribution. Zaleplon with its ultra-short half-life has been detected in few clinical or forensic cases possibly due to assay unavailability, low frequency of use, and short window of detection. Though Z-drugs have improved pharmacokinetic profiles, their adverse effects, neuropsychiatric sequelae, and incidence of poisoning and death may prove to be similar to older hypnotics.

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Section: Analysis and Detection Of Z-drugsmentioning

confidence: 99%

Section: Clinical Toxicology Of Z-drugsmentioning

confidence: 99%

Section: Analysis and Detection Of Z-drugsmentioning

confidence: 99%

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The Clinical and Forensic Toxicology of Z-drugs

Gunja

2013

J. Med. Toxicol.

164

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“…This highly selective assay achieved a LLOQ of 0.5 ng/ml, equivalent to the sensitivity of an LC/MS technique, by exploiting the native fluorescence of ziprasidone. Tonon and Bonato [14] thoroughly reviewed analysis of nonbenzodiazepine hypnotic drugs in various biological matrices. The quantification of zopiclone, zolpidem and zalepon (Z-drugs) were covered with the focus on sample preparation procedures and separation techniques used.…”

Section: Mental Disordersmentioning

confidence: 99%

Quantitative Analysis of Drugs in Biological Matrices by HPLC Hyphenated to Fluorescence Detection

Lipka

Vaccher

2015

Bioanalysis

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An overview of the state-of-the art in HPLC coupled with fluorescence detection is presented. Over the last 20 years, the increasing number of methodological papers on this topic (4082 between 1994 and 2004 and 7725 between 2004 and 2014) is testament to its utility in bioanalytical applications. Compared with conventional UV absorbance detection used in HPLC, fluorescence detection can greatly enhance the sensitivity leading to limits of detection similar to those obtained with mass spectrometry, offering researchers a sensitive, robust and relatively inexpensive instrumental method. This work will focus on the analysis of pharmaceutical compounds in different biological matrices, either naturally fluorescent or derivatized with a fluorescent agent, and some of them chiral. Therapeutic applications, sample preparation and derivatization, sensitivity for each example are described.

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“…Many methods dealing with the determination of both analytes by HPLC with different detectors have been reported . Determination of the analytes in human plasma by RP HPLC with UV or fluorescence detection has been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Development of an SPE method for the determination of zaleplon and zopiclone in hemolyzed blood using fast GC with negative-ion chemical ionization MS

2014

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An SPE procedure for the determination of zaleplon and zopiclone in low-volume human hemolyzed blood using fast GC with negative-ion chemical ionization MS has been developed and validated. Both analytes were well retained on Oasis MCX and HLB columns, and sufficient extraction efficiency was achieved at pH 9.0. For further study a hydrophilic-lipophilic 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 show that the developed method is accurate, selective, precise, and very fast with excellent recovery and low LOD and LOQ.

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Methods For The Analysis of Nonbenzodiazepine Hypnotic Drugs in Biological Matrices

Cited by 8 publications

References 79 publications

The Clinical and Forensic Toxicology of Z-drugs

The Clinical and Forensic Toxicology of Z-drugs

Quantitative Analysis of Drugs in Biological Matrices by HPLC Hyphenated to Fluorescence Detection

Development of an SPE method for the determination of zaleplon and zopiclone in hemolyzed blood using fast GC with negative-ion chemical ionization MS

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