Maternal exposure to zolpidem and risk of specific birth defects.

Zolpidem is a non-benzodiazepine agent indicated for treatment of insomnia. While zolpidem crosses the placenta, little is known about its safety in pregnancy. We assessed associations between self-reported zolpidem use 1 month before pregnancy through to the end of the third month ("early pregnancy") and specific birth defects using data from two multi-site case-control studies: National Birth Defects Prevention Study and Slone Epidemiology Center Birth Defects Study. Analysis included 39,711 birth defect cases and 23,035 controls without a birth defect. For defects with ≥ 5 exposed cases, we used logistic regression with Firth's penalised likelihood to estimate adjusted odds ratios and 95% confidence intervals, considering age at delivery, race/ethnicity, education, body mass index, parity, early-pregnancy antipsychotic, anxiolytic, antidepressant use, early-pregnancy opioid use, early-pregnancy smoking, and study as potential covariates. For defects with three-four exposed cases, we estimated crude odds ratios and 95% confidence intervals. Additionally, we explored differences in odds ratios using propensity score-adjustment and conducted a probabilistic bias analysis of exposure misclassification. Overall, 84 (0.2%) cases and 46 (0.2%) controls reported early-pregnancy zolpidem use. Seven defects had sufficient sample size to calculate adjusted odds ratios, which ranged from 0.76 for cleft lip to 2.18 for gastroschisis. Four defects had odds ratios > 1.8. All confidence intervals included the null. Zolpidem use was rare. We could not calculate adjusted odds ratios for most defects and estimates are imprecise. Results do not support a large increase in risk, but smaller increases in risk for certain defects cannot be ruled out.

Alcohol spiked with zolpidem and midazolam potentiates inflammation, oxidative stress and organ damage in a mouse model.

PURPOSE: Crime-related spiking of alcoholic drinks with prescription drugs is quite common and has been happening for centuries. This study, therefore, evaluated the effects of oral administration of alcohol spiked with the zolpidem and midazolam potent sedatives on inflammation, oxidative stress and various organ damage in male Swiss albino mice. METHODS: Mice were randomly assigned into six treatment groups; the first group constituted the normal control, the second group received 50 mg/kg body weight of zolpidem only, the third group received 50 mg/kg body weight zolpidem dissolved in 5 g/kg alcohol, the fourth group received 50 mg/kg midazolam only, the fifth group received midazolam (50 mg/kg) dissolved in 5 g/kg alcohol and the sixth group received 5 g/kg alcohol. RESULTS: Alcohol-induced significant reduction in neurological function and altered blood hematological indicators. Such neurological impairment and negative effects on blood were exacerbated in mice administered with spiked alcohol. Additionally, midazolam and zolpidem enhanced alcohol-driven elevation of liver function markers; the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) gamma glutamyltransferase (GGT), total bilirubin and alkaline phosphatase. Exposure to alcohol and/or spiked alcohol led to significant augmentation of nitric oxide and malonaldehyde, with concomitant depletion of liver glutathione (GSH) levels. Similarly, serum levels of pro-inflammatory cytokines tumor necrosis factor alpha and interferon-gamma were increased by co-exposure with midazolam or zolpidem. Alcohol-induced hepatotoxicity and nephrotoxicity were amplified by exposure to alcohol spiked with midazolam/zolpidem. CONCLUSION: Exposure to alcohol spiked with midazolam or zolpidem appears to exacerbate neurological deficits, inflammation, oxidative stress, and organ damage.

Immediate Postoperative Zolpidem Use Increases Risk of Falls and Implant Complication Rates Following Total Hip Arthroplasty: A Retrospective Case-Control Analysis.

BACKGROUND: Zolpidem is the most widely used hypnotic in the United States and has known side effects. However, the morbidity of zolpidem use following total hip arthroplasty (THA) is not well-defined. Thus, the aim of this study was to assess the effects that zolpidem use has on medical and implant complications, falls, lengths of stay, and medical utilizations following THA. METHODS: A retrospective query of a nationwide insurance claims database was conducted from 2010 to 2020. All cases of THA and hypnotic use were identified using procedural and national drug codes. Patients who were prescribed zolpidem within 90 days of surgery were matched to hypnotic naive patients 1:5 based on demographic and comorbidity profiles. The 90-day medical complications, falls, fragility fractures, costs, and readmission rates, as well as 2-year implant complications were compared between cohorts. A total of 50,328 zolpidem patients were matched to 251,286 hypnotic naive patients. RESULTS: The zolpidem group had significantly higher rates of medical complications, falls, and fragility fractures when compared to the hypnotic-naive group. The zolpidem group had significantly higher rates of dislocation, mechanical loosening, and periprosthetic fracture. Likewise, healthcare utilization was significantly greater in the zolpidem group. CONCLUSION: Zolpidem use following THA is associated with significant risk of medical and implant complications, as well as fall risks, increased costs, lengths of stay, and readmissions. The findings of this study may affect discussions between orthopaedic surgeons and their patients on the benefits of sleep quality in their recovery versus the incurred risks of zolpidem use. LEVEL OF EVIDENCE: III, retrospective case-control study.

Rapid resolution of catatonia secondary to post traumatic stress disorder with secondary psychotic features through scheduled zolpidem tartrate.

Catatonia is a complication of numerous psychiatric and medical conditions. The first-line treatment is typically management of the underlying primary condition as well as scheduled benzodiazepines or electroconvulsive therapy. Electroconvulsive therapy and benzodiazepines are not always tolerated or available when treating patients with catatonia. For this reason, other treatment regimens have been trialed in recent years, including the GABA-modulatory Z drugs such as zolpidem. Some alternative treatment modalities have shown great promise. However, which populaces these are most beneficial for is still unclear. In this article, we examine a case report of a woman who suffered from post-traumatic stress disorder with secondary psychotic features who experienced recurrent akinetic catatonia that was refractory to benzodiazepine therapy. She responded rapidly to scheduled zolpidem with minimal side effects. It is our author's belief that when managing catatonia in patients with post traumatic stress disorder with secondary psychosis, Z drugs may be preferable to benzodiazepines.

Simultaneous Analysis of Zolpidem, Four Hydroxyzolpidems and Two Zolpidem Carboxylic Acids in Postmortem Urine Using Liquid Chromatography--Tandem Mass Spectrometry.

Zolpidem (ZOL) is a short-acting hypnotic that is sometimes used in drug-facilitated crimes such as sexual assaults, robbery and homicides. Therefore, it is important to understand the metabolism of ZOL. This study quantified ZOL and its metabolites, including two carboxylic acids (zolpidem phenyl-4-carboxylic acid [M1] and 6-carboxylic acid [M2]) and four hydroxyzolpidems (4-(hydroxymethyl)phenyl zolpidem [M3], 6-hydroxymethyl zolpidem [M4], 7-hydroxyzolpidem [7OH] and 8-hydroxyzolpidem [8OH]) in postmortem urine using liquid chromatography--triple quadrupole mass spectrometry. The concentration of M1 was highest in all cases, followed by total 7OH in five of six samples. The concentrations of M2 and total M4 were relatively high. Most of M4 and 8OH were excreted as conjugates, whereas up to 55% of 7OH was excreted in its free form. Peaks corresponding to zolpidem dihydrodiol (ZHDH), dihydro(hydroxy)zolpidem cysteine adduct (DHZCys) and zolpidem cysteine adduct (ZCys) were also detected in all the urine samples. ZDHD was excreted as conjugates, whereas almost all DHZCys and ZCys were in their free form.

Qualitative analysis of 7- and 8-hydroxyzolpidem and discovery of novel zolpidem metabolites in postmortem urine using liquid chromatography-tandem mass spectrometry.

PURPOSE: Zolpidem (ZOL) is a hypnotic sometimes used in drug-facilitated crimes. Understanding ZOL metabolism is important for proving ZOL intake. In this study, we synthesized standards of hydroxyzolpidems with a hydroxy group attached to the pyridine ring and analyzed them to prove their presence in postmortem urine. We also searched for novel ZOL metabolites in the urine sample using liquid chromatography-triple quadrupole mass spectrometry (LC-QqQMS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QqTOFMS). METHODS: 7- and 8-Hydroxyzolpidem (7OHZ and 8OHZ, respectively) were synthesized and analyzed using LC-QqQMS. Retention times were compared between the synthetic standards and extracts of postmortem urine. To search for novel ZOL metabolites, first, the urine extract was analyzed with data-dependent acquisition, and the peaks showing the characteristic fragmentation pattern of ZOL were selected. Second, product ion spectra of these peaks at various collision energies were acquired and fragments that could be used for multiple reaction monitoring (MRM) were chosen. Finally, MRM parameters were optimized using the urine extract. These peaks were also analyzed using LC-QqTOFMS. RESULTS: The presence of 7OHZ and 8OHZ in urine was confirmed. The highest peak among hydroxyzolpidems was assigned to 7OHZ. The novel metabolites found were zolpidem dihydrodiol and its glucuronides, cysteine adducts of ZOL and dihydro(hydroxy)zolpidem, and glucuronides of hydroxyzolpidems. CONCLUSIONS: The presence of novel metabolites revealed new metabolic pathways, which involve formation of an epoxide on the pyridine ring as an intermediate.

Potentially Inappropriate Medication Use in Patients with Dementia.

The objective of this study was to characterize the epidemiology of using potentially inappropriate medications associated with dementia exacerbation (DPIMs) in elderly outpatients with dementia. Electronic medical records were retrospectively reviewed for geriatric patients with dementia who were prescribed at least one medication in 2016 at a tertiary, university-affiliated hospital. The 2015 Beers criteria were used to define DPIMs. Logistic regression was performed to identify factors associated with prescribing DPIMs in patients with dementia. Among 2100 patients included in our study, 987 (47.0%) patients were prescribed at least one DPIM. Benzodiazepines were the most frequently prescribed DPIM followed by anticholinergics, histamine H2-receptor blockers, and zolpidem. The risk of prescribing DPIMs was significantly increased in female patients (odds ratio (OR) 1.355) with polypharmacy (OR 5.146) and multiple comorbidities (OR 1.129) (p < 0.05 for all). Coexistence of Parkinson's disease (OR 1.799), mood disorder (OR 1.373), or schizophrenia (OR 4.116) in patients with dementia further increased the likelihood of receiving DPIMs. In conclusion, DPIMs were commonly used in elderly patients with dementia in Korea with benzodiazepines most frequently prescribed followed by anticholinergics. Female patients using polypharmacy with multiple comorbidities should be closely monitored to minimize unnecessary DPIM use and, ultimately, DPIM-related harms.

Development and evaluation of a 3D printing protocol to produce zolpidem-containing printlets, as compounding preparation, by the pressurized-assisted microsyringes technique.

Insomnia is a chronic disorder with a mean prevalence ranged from 6% to 15% worldwide. The usual pharmacologic treatment for insomnia has been benzodiazepines and barbiturates. More recently, z-drugs were introduced in the therapeutic arsenal to maximize benefits and minimize treatment damage. Zolpidem tartrate, whose primary indication is for sleep initiation problems, is conventionally used at a recommended dose of 5 mg for women as well as elderly patients (<65 years-old) and 10 mg for non-elderly men. However, it was demonstrated that the dose of zolpidem should be adjusted according to the gender, age, condition of the patient and the presence of polypharmacy to decrease the occurrence of adverse events. Faced with the therapeutic limitations inherent to marketed products, magistral preparations offer medical and legal alternatives to mass treatment. The use of a semi-automatic technique, with standardized protocol, such as 3D printing should be advantageously implemented as an alternative to standard compounding procedures. In this work, the pressure-assisted microsyringes method was selected as it allows the tridimensional printing, and so the customization of the dose, by easily extruding a viscous semi-liquid material, called "slurry", through a syringe at room temperature. It has been demonstrated that this methodology allows obtaining printlets that responded to the zolpidem-containing tablets monograph of the US pharmacopoeia Edition 42. The compounding preparations proposed in this work therefore have the same criteria of requirements as a commercial form.

Orthopedic sleep and novel analgesia pathway: a prospective randomized controlled trial to advance recovery after shoulder arthroplasty.

BACKGROUND: Lack of sleep is associated with adverse effects on postsurgical pain and recovery. We hypothesized that a multimodal sleep pathway, including nonpharmacologic sleep hygiene interventions and the use of zolpidem and melatonin, could improve patient analgesia and sleep after total shoulder arthroplasty. METHODS: We performed a prospective randomized controlled study in which patients undergoing anatomic and reverse total shoulder arthroplasty were treated with or without an interventional multimodal sleep pathway. This pathway included nursing-directed nonpharmacologic measures that promote sleep hygiene and pharmacologic interventions with low-dose zolpidem and melatonin at bedtime. All patients underwent a standardized multimodal analgesia protocol with scheduled acetaminophen, naproxen, and gabapentin, as well as a single-shot interscalene regional nerve block. RESULTS: This study enrolled 125 patients (64 in control group and 61 in interventional group) with similar demographic characteristics. The interventional group showed less oral morphine milligram equivalent (MME) consumption on postoperative day (POD) 0 (44.8 ± 36.1 MMEs vs. 60.9 ± 42.1 MMEs, P = .01) and showed a trend toward lower POD 0 visual analog scale pain scores (2.6 ± 1.8 vs. 3.3 ± 3.0, P = .06). Visual analog scale pain scores and MME consumption were similar on POD 1. The interventional group showed a longer objective sleep duration by quantitative wrist actigraphy (5.9 ± 3.1 hours vs. 4.6 ± 2.7 hours, P = .008), with better sleep quality assessed by the Leeds Sleep Evaluation Questionnaire (0-100 scale; 50.3 ± 26.8 vs. 38.5 ± 27.8, P = .01). The 2 groups showed similar satisfaction with pain management (89.2% vs. 79.6%, P = .16) and sleep management (82.1% vs. 76.8%, P = .48). There was no difference in the length of inpatient stay (32.2 ± 14.8 hours vs. 34.1 ± 12.8 hours, P = .44). CONCLUSION: In the setting of a regional and multimodal analgesia recovery plan for shoulder arthroplasty patients undergoing inpatient observation, the use of an interventional sleep pathway appears to be safe and beneficial, with improved analgesia, reduced opioid use, increased sleep duration, and improved reported sleep quality during the postoperative recovery period.

The Effect of Improving Preoperative Sleep Quality on Perioperative Pain by Zolpidem in Patients Undergoing Laparoscopic Colorectal Surgery: A Prospective, Randomized Study.

METHODS: A prospective, randomized study was conducted with 88 patients undergoing laparoscopic colorectal surgery. The experimental group (S group, n = 44) was given 10 mg of zolpidem tartrate one night before the surgical procedure, while no medication was given to the control group (C group, n = 44). The primary outcome was the intraoperative remifentanil consumption. Sufentanil consumption, average patient-controlled analgesia (PCA) effective press times, the visual analog scale (VAS) scores, and incidences of postoperative nausea and vomiting (PONV) were recorded at 6 h (T1), 12 h (T2), and 24 h (T3) postoperatively. RESULTS: The intraoperative remifentanil consumption was significantly lower in the S group than that in the C group (p < 0.01). Sufentanil consumption at 6 h and 12 h postoperatively was significantly lower in the S group than that in the C group (p < 0.05); average PCA effective press times and VAS scores, at 6 h and 12 h postoperatively, were significantly lower in the S group than those in the C group (p < 0.01); differences between groups 24 h postoperatively were not significant. No significant between-group difference was noted in the incidence of nausea and vomiting. CONCLUSION: Improving patients' sleep quality the night before surgical procedure by zolpidem can decrease the usage of intraoperative analgesics and reduce postoperative pain.

Zolpidem improves patients' sleep quality after surgical treatment for infective endocarditis: a prospective observational study.

PURPOSE: The objective of this study was to investigate the efficacy of zolpidem for improving post-operative sleep quality among patients with infective endocarditis (IE) and to identify the potential risk factors for impaired sleep quality at 6 months after surgery. METHODS: Patients with IE who underwent surgical treatment were divided into two groups according to zolpidem usage. The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate patients' sleep quality and daytime sleepiness at baseline, which was the second day after transferal, and at 6 months after surgery. Logistic regression was used to identify potential risk factors. RESULTS: There were 32 patients in the zolpidem group and 42 in the control group. The PSQI and ESS scores at 6 months after surgery were significantly lower than those at baseline in both groups (P = 0.04). Additionally, 9 patients (28%) in the zolpidem group and 22 patients (52%) in the control group suffered poor sleep quality. Multivariate analysis identified age (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.12-1.42), baseline PSQI score (OR = 2.66, 95%CI: 1.55-4.65), and no zolpidem usage (OR = 45.48, 95%CI: 3.01-691.23) as independent factors for poor sleep quality. CONCLUSIONS: Poor sleep quality after IE surgery was prevalent among patients even 6 months after IE surgery. Age, baseline PSQI score and no zolpidem usage were independently associated with poor sleep quality. Therefore, zolpidem has the potential to be an effective part of a treatment arsenal for poor sleep quality after surgical treatment for IE.

Cognitive and balance dysfunctions due to the use of zolpidem in the elderly: a systematic review / Alterações cognitivas e de equilíbrio devido ao uso de zolpidem em idosos: uma revisão sistemática

ABSTRACT. Zolpidem is one of the most widely prescribed hypnotic (non-benzodiazepine) agents for sleep disorder. Recently, an increase in the demand for this drug has been observed, mainly in the elderly population. Objective: This study aims to analyze the acute effect of zolpidem on cognitive and balance dysfunctions in the elderly population. Methods: A study was conducted by two independent researchers in four virtual scientific information bases and included randomized controlled trials. The studies evaluated elderly patients using zolpidem. Cognitive and balance dysfunctions were analyzed. Results: Six articles were included. The mean age of the participants in the studies was 69 years. The following zolpidem dosages were evaluated: 5, 6.25, 10, and 12.5 mg. Comparing zolpidem and placebo, relating to the cognitive dysfunctions, there is no statistically significant difference between the groups. However, in relation to balance dysfunctions, there is a statistically significant difference between the intervention and the comparison, favoring placebo. Conclusions: Zolpidem, even in usual doses (5 mg and 10 mg), has shown to increase the risk for balance dysfunctions. However, this does not occur in relation to cognitive changes.

RESUMO. Zolpidem é um dos agentes hipnóticos (não benzodiazepínicos) mais prescritos para o manejo dos distúrbios do sono. Recentemente, observou-se um aumento na demanda por esse medicamento, principalmente pela população idosa. Objetivo: Este estudo visa analisar o efeito agudo do zolpidem em relação às alterações cognitivas e de equilíbrio na população idosa. Métodos: Uma busca em quatro bases de informação científica virtual foi feita por dois pesquisadores independentes e incluiu ensaios clínicos randomizados. Os estudos avaliaram o uso de zolpidem em pacientes idosos. Alterações cognitivas e de equilíbrio foram analisadas. Resultados: Seis artigos foram incluídos. A média de idade entre os estudos foi de 69 anos. As seguintes posologias foram analisadas: 5; 6,25; 10; e 12,5 mg. Em relação às alterações cognitivas, comparando-se zolpidem com placebo, não há diferença estatisticamente significativa entre os grupos. Entretanto, no desfecho alterações de equilíbrio, há diferença estatisticamente significativa entre intervenção e comparação, a favor do placebo. Conclusões: Zolpidem, mesmo em doses usuais (5 e 10 mg), mostrou aumentar o risco para alterações de equilíbrio, entretanto, isso não ocorre em relação às alterações cognitivas.

Macroscopic identification of visceral titanium pigment in an intravenous drug user.

Autopsy findings in intravenous drug addicts are quite variable and may involve a number of organ systems. Reports of the macroscopic identification at autopsy of components of tablets that have been crushed and injected are, however, exceedingly rare. The case of 34-year-old man who died of zolpidem toxicity on a background of pulmonary hypertension attributed to intravenous injections of crushed tablets is described. A very unusual finding was very fine white stippling on the cut surfaces of both the liver and spleen which was shown on energy-dispersive x-ray spectroscopy (EDS) to be titanium dioxide most likely from the coating of the zolpidem tablets. This case is significant in demonstrating titanium dioxide accumulation within organs at both macroscopic and microscopic levels, with confirmation of exposure by EDS analysis. The clinical significance of exposure to such high levels of titanium dioxide is unclear.

The Risk of Overdose With Concomitant Use of Z-Drugs and Prescription Opioids: A Population-Based Cohort Study.

OBJECTIVE: The Z-drugs (zolpidem, zopiclone, zaleplon) are widely used to treat insomnia in patients receiving prescription opioids, and the risk of overdose resulting from this coprescription has not been explored. The authors compared the rates of overdose among patients using opioids plus Z-drugs and patients using opioids alone. METHODS: All individuals 15 to 85 years of age receiving prescription opioids, regardless of underlying indication and without evidence of cancer, were identified in the IBM MarketScan database (2004-2017). Patients with concomitant exposure to Z-drugs were matched 1:1 to patients with exposure to prescription opioids alone based on opioid prescribed, morphine equivalents, number of days' supply, and hospitalization within the past 30 days. The primary outcome was any hospitalization or emergency department visit due to an overdose within 30 days, using an intention-to-treat approach. Fine stratification on the propensity score was used to control for confounding. RESULTS: A total of 510,529 exposed patients and an equal number of matched reference patients were analyzed. There were 217 overdose events among the exposed patients (52.5 events per 10,000 person-years) and 57 events among the reference patients (14.4 events per 10,000 person-years), corresponding to an unadjusted hazard ratio of 3.67 (95% CI=2.75, 4.90). Using fine stratification on the propensity score (c-statistic: 0.66), the adjusted hazard ratio was 2.29 (95% CI=1.79, 2.91). Results were consistent across sensitivity analyses. CONCLUSIONS: Among patients receiving prescription opioids, after controlling for all confounding factors, concomitant treatment with Z-drugs was associated with a substantial relative increase in the risk of overdose. The potential implications are significant given the large number of opioid-treated patients receiving Z-drugs.

Determination of zolpidem phenyl-4-carboxylic acid and zolpidem 6-carboxylic acid in hair using gas chromatography-electron ionization-tandem mass spectrometry.

A gas chromatography-electron ionization-tandem mass spectrometric (GC-EI-MS/MS) method was developed and validated for determination of the major metabolites of zolpidem, zolpidem phenyl-4-carboxylic acid (ZPCA) and zolpidem 6-carboxylic acid (ZCA) in human hair. The sample preparation procedure involves decontamination, mechanical pulverization, incubation, extraction and purification prior to instrumental analysis. The extracts were derivatized using hexafluoroisopropanol and heptafluorobutyric anhydride and analyzed by GC-EI-MS/MS. The linear ranges were 8-100 pg/mg for ZPCA and 16-200 pg/mg for ZCA, with the correlation coefficients >0.997. The limits of detection were 1.8 pg/mg for ZPCA and 1.7 pg/mg for ZCA. The recoveries ranged from 77.6 to 111.7%. The intra- and inter-day precisions were within 16.9 and 11.7%, while intra- and inter-day accuracies were -7.0-8.7 and -2.8-7.8%, respectively. The developed method was applied for the analysis of forensic hair samples obtained from suspected zolpidem abusers and the following concentration ranges were monitored: ZPCA 11.9-35.9 pg/mg and ZCA 16.6-21.8 pg/mg. The method proved to be suitable for picogram-level determination of ZPCA and ZCA in human hair.

Supramolecular solvent (SUPRASs) extraction method for detecting benzodiazepines and zolpidem in human urine and blood using gas chromatography tandem mass spectrometry.

OBJECTIVE: A high-throughput and sensitive method using supramolecular solvent (SUPRASs) for detecting 9 benzodiazepines and zolpidem in human urine and blood by gas chromatography-tandem mass spectrometry (GC-MS/MS) was newly established and applied to authentic human urine and blood samples in this study. METHODS: Urine and blood samples were subjected to liquid-liquid extractions with supramolecular solvent mixture which consists of tetrahydrofuran and 1-hexanol. The solvent layer was evaporated to dryness by stream of nitrogen. The residue was reconstituted with methanol, and subjected to analysis by GC-MS/MS in multiple reaction monitoring (MRM) mode; internal standard method was employed for quantifying of each targeted compound. RESULTS: The regression equation has a good linear relationship with correlation coefficients for all tested compounds were not lower than 0.9991. The lower limits of the quantification ranged from 0.20 to 5 ng/mL for tested compounds in urine; Meanwhile, the lower limits of the quantification in this method ranged from 1 to 50 ng/mL for tested compounds in blood. These results showed that excellent reproducibility and satisfactory extraction recovery rates could be obtained for the established analytical method for 10 drugs in both blood and urine samples. CONCLUSION: The established method in this study was high-throughput, simple and sufficiently sensitive for determining of benzodiazepinesand zolpidem in human urine and blood. Therefore, this newly established method could be of use for qualitative and quantitative determination of such drugs in urine and blood samples either for clinical poisoning monitoring or for forensic identification.