Click title links to access full-text
Analysis of Zolpidem in Postmortem Fluids and Tissues Using Ultra-Performance Liquid Chromatography–Mass Spectrometry
Zolpidem is a nonbenzodiazepine sedative hypnotic drug used for the short-term treatment of insomnia. While quite effective in producing sedation, zolpidem has potentially hazardous side effects when put in the context of complex tasks. Therefore, to more fully understand the postmortem concentrations of zolpidem, our laboratory has developed a sensitive method for the quantitation of zolpidem in biological specimens. Additionally, we have evaluated the distribution of zolpidem in various postmortem tissues and fluids from 10 aviation fatalities. This method incorporated a modified acetonitrile ‘crash and shoot’ extraction and a Waters Xevo TQ-S with an Acquity ultra-performance liquid chromatograph. The linear dynamic range was 0.4–800 ng/mL. The extraction efficiencies ranged from 78 to 87%, depending on the concentration. Postmortem blood zolpidem concentrations in these 10 cases ranged from 7.6 to 76.5 ng/mL. The highest concentrations of zolpidem present in each victim were found in the liver, spleen, lung and kidney tissues. Distribution coefficients for zolpidem were determined for each of the specimen types analyzed. These coefficients are expressed relative to the blood concentration in each case. This method proved to be simple, accurate and robust for the identification and quantitation of zolpidem in postmortem fluids and tissues.
Determining Zolpidem Compliance: Urinary Metabolite Detection and Prevalence in Chronic Pain Patients
Zolpidem (Ambien®) is the most prescribed insomnia treatment in the USA; however, little is known about zolpidem metabolite excretion in chronic pain patients. As zolpidem is extensively metabolized in vivo to zolpidem 4-phenyl carboxylic acid (ZCA), metabolite detection may provide improved accuracy for compliance determinations, thereby improving clinical decisions. Zolpidem and ZCA were extracted from 1 mL human urine by mixed-mode solid-phase extraction. Samples were analyzed by LC–MS-MS using positive electrospray ionization with multiple reaction monitoring mode employed for detection and quantification. Gradient chromatographic separation was achieved with a reversed-phase column in a rapid 1.8 min analysis. The assay was linear from 4 to 1,000 µg/L for zolpidem and 4 to 10,000 µg/L for ZCA. Interday recovery (bias) and imprecision (n = 20) were 100–107% of target and 2.4–3.7% relative standard deviation, respectively. Extraction efficiencies were 78–90%. Pain compliance samples (n = 3,142) were de-identified and analyzed for zolpidem and ZCA. Zolpidem was detected greater than limit of quantification in 720 specimens (22.9%), while ZCA was detected in 1,579 specimens (50.3%). Only five specimens contained zolpidem alone. ZCA was observed without parent zolpidem in 864 specimens, thereby increasing population detection rates by 27.5%. Addition of a zolpidem metabolite to compliance determinations substantially improved detection for zolpidem intake and also should prove useful in clinical and forensic settings.
Brisbane Times Kristian Silva October 7, 2014
A man accused of drugging and raping a backpacker near Stanthorpe last year has been refused bail.
Police allege the 47-year-old Annerley man laced chocolate with the drug Zolpidem, after luring the German tourist to the Stanthorpe area with the promise of a job.
Police say the 20-year-old victim met the man after catching a bus to the Stanthorpe on August 13 last year, after responding to an online nanny advertisement.
Curr Drug Saf. 2014 Jun 1; DOI: 10.2174/1574886309666140601210422
Study objectives. Sleep maintenance problems are common, hence treatments enabling patients to fall asleep more rapidly after middle-of-the-night (MOTN) awakenings, without impairing next morning alertness, are needed. This literature review compares the effects of MOTN administration of various hypnotics on morning driving ability, a potentially dangerous daily activity under conditions of impairment. Methods. A literature search was conducted identifying on-the-road driving studies examining the effects of MOTN administration of hypnotics on morning driving performance. In a standardized 100-km highway driving test in normal traffic, subjects were instructed to drive with a steady lateral position and constant speed of 95 km/h. The primary outcome measure of the driving test is the Standard Deviation of Lateral Position (SDLP, cm), i.e. weaving of the car. Results. Four driving studies were identified. Driving performance after MOTN administration of traditional benzodiazepine hypnotics was not examined. Zolpidem (10 mg and 20 mg, oral immediate release tablets) significantly impaired driving in a dose-dependent manner, when tested 4 hours after MOTN administration. Also, gaboxadol (15 mg) and zopiclone (7.5 mg) significantly impaired next-morning driving after MOTN administration. In contrast, sublingual zolpidem (3.5 mg) and zaleplon (10 mg and 20 mg) did not significantly affect driving 4 hours after MOTN administration. Conclusions. Driving was not affected 4 hours after MOTN administration of sublingual zolpidem (3.5 mg) or zaleplon (10 mg and 20 mg). Significant driving impairment was found after MOTN administration of zolpidem (10 and 20 mg), gaboxadol (15 mg), and zopiclone (7.5 mg).
Request a copy of the article (QH Staff only)
ABC News Madeleine Morris 19 March 2014
The practice of mixing sleeping pills with alcohol and energy drinks is widespread in the National Rugby League, a club doctor has told the ABC.
John Mayhew, the doctor for the Auckland-based New Zealand Warriors, says he also believes the problem is widespread in other codes.
His comments come as the NRL begins testing players for the sleeping pill Stilnox and other prescription drugs, in addition to existing tests for steroids and other performance-enhancing substances.
PLoS ONE 2013; 8(6): e67459; DOI 10.1371/journal.pone.0067459
BACKGROUND: While an association between zolpidem use and fracture and road accident was previously proposed, this study aimed to further explore the frequency and risk of a wide spectrum of injuries in subjects prescribed with zolpidem in Taiwan. METHODS: We identified 77,036 subjects who received Zolpidem treatment between 2005 and 2007. We randomly selected 77,036 comparison subjects who were frequency-matched based-on their demographic profiles. We individually tracked each subject for a 90-day period to identify those who subsequently suffered an injury. Cox proportional hazards regressions were performed to calculate the hazard ratio of injury between the two groups. RESULTS: The incidence rate of injury during the 90-day follow-up period for the total subjects was 18.11 (95% CI = 17.69-18.54) per 100 person-years; this was 24.35 (95% CI = 23.66-25.05) and 11.86 (95% CI = 11.39-12.36) for the study and comparison cohort, respectively. After adjusting for demographic variables, the hazard ratio (HR) of injury during the 90-day follow-up period for study subjects was 1.83 (95% CI = 1.73-1.94) that of comparison subjects. Additionally, compared to comparison subjects, the adjusted HR of injury during the 90-day follow-up period for study subjects who were prescribed Zolpidem for >30 days was as high as 2.17 (95% CI = 2.05-2.32). The adjusted HR of injury to blood vessels for study subjects was particularly high when compared to comparison subjects (HR = 6.34; 95% CI = 1.37-29.38). CONCLUSIONS: We found that patients prescribed with Zolpidem were at a higher risk for a wide range of injuries.
Click here to read full text
Sydney Morning Herald Steve Larkin & Rob Forsaith 22 February 2013
Eamon Sullivan apologised for being a ringleader as he and five other top Australian swimmers admitted lying about taking a banned drug before the London Olympics.
All six men’s freestyle relay swimmers, including world champion James Magnussen, could be banned from future Olympics for their abuse of the banned sedative Stilnox.
Brisbane Times Bradley Partridge & Wayne Hall 25 February 2013
Zolpidem (sold as Stilnox in Australia) is a prescription drug for the treatment of insomnia. So what role does it play in the lives of elite athletes?
In elite sports that require frequent international travel, such as swimming, Stilnox may be prescribed to help athletes cope with changes in their sleep cycle.
Stilnox is used for related reasons in other professional sporting leagues.