Zaleplon (Sonata(R)) Analysis in Postmortem Specimens by Gas Chromatography--Electron Capture Detection

Abstract

Zaleplon (Sonata) is a sedative hypnotic prescription medication used for the short-term treatment of insomnia. Although Zaleplon was approved by the FDA in 1999, there has been limited postmortem information about the drug cited in the toxicology literature. Zaleplon was separated from postmortem biological specimens utilizing liquid-liquid extraction coupled with a solid-phase extraction technique, and detection was accomplished by a gas chromatography-electron capture detector. The method was linear from 5.0 to 150 ng/mL with the limit of quantitation and detection determined to be 3.0 and 0.50 ng/mL, respectively. The postmortem tissue distribution of zaleplon in seven cases was as follows: 6.1-1490 ng/mL central blood (seven cases), < 3.0-503 ng/mL femoral blood (five cases), 108 ng/mL harvest blood (one case), 343-679 ng/g liver (four cases), 950 ng/g spleen (one case), < 3.0-85 ng/mL bile (three cases), 3.8-106 ng/mL urine (four cases), < 3.0-486 ng/mL vitreous humor (five cases), and 0.005-3.4 mg total gastric contents (four cases). A validated method for the analysis of zaleplon and postmortem concentrations of autopsy specimens are reported to aid the forensic toxicologist with interpretation of future casework.

The Clinical and Forensic Toxicology of Z-drugs

“…With PMR, drugs diffuse rapidly across membranes and tissues after death causing differential concentrations between central and peripheral blood compartments. Both zolpidem and zaleplon exhibit significant PMR, though this seems to be low or negligible for zopiclone [48,[66][67][68]. Zolpidem has been reported to have a central to peripheral blood concentration ratio of 3.74 in postmortem specimens, though previous studies have had lower values [48].…”

“…Polydrug overdose is a major confounder in deciding whether the fatalities are attributable to detected Z-drugs. Although there have been several reported fatalities where zaleplon has been ingested along with other drugs, none have been solely attributable to zaleplon [66,82]. This may represent lower zaleplon use or difficulties in measuring zaleplon levels due to its ultra-short half-life and rapid antemortem metabolism.…”

Development of Stability Indicating Densitometric and Enhanced sensitivity Spectrofluorimetric Methods for Determination of Zaleplon in Presence of its Acidic Degradation Products

“…It has an empirical formula of C 17 H 15 N 5 O and a molecular weight of 305.34 g/mol [1]. It is chemically unrelated to the benzodiazepine class of medications for sleep, but it has similar effects.…”

“…The literature survey reveals several methods for determination of Zaleplon in plasma [4][5][6][7][8][9], hair and oral fluids [10,11], blood [12][13][14], human urine [15] and in postmortem specimen [1,16]. It was also determined in capsules by voltammetric method [17] and in tablets by reversed phase high performance liquid chromatographic (RP-HPLC) method [18].…”

Simultaneous determination of drugs in human autopsy material using phase‐optimized liquid chromatography

“…The screening method was started with about 50 compounds that were proved in the examined cases. Procedures utilized for the initial detection of drugs in a biological sample employ a variety of analytical techniques: immunoassays (Gorczynski and Melbye, ), gas chromatography/mass spectrometry (GC‐MS; Paterson et al , ; Anderson and Budd, ), liquid chromatography/ultraviolet diode‐array (HPLC‐UV‐DAD; Herzler et al , ), and HPLC/ mass spectrometry (LC‐MS; Venisse et al , ; Drummer, ; Gergov et al , ; Yao et al , ; Johnson and Botch, ). Immunoassay techniques are restricted to a specific and limited list of compounds.…”