Direct injection ultra-performance liquid chromatography-tandem mass spectrometry for the high-throughput determination of etomidate and etomidate acid in wastewater.

Etomidate (ET), a hypnotic agent used for the induction of anesthesia, is rapidly metabolized to etomidate acid (ETA) in the liver. Recently, ET has become one of the most serious alternative drugs of abuse in China. Therefore, an urgent need exists to develop a fast and convenient analysis method for monitoring ET. The current work presents a simple, fast, and sensitive direct injection method for the determination of ET and ETA in wastewater. After the optimization of the ultra-performance liquid chromatography-tandem mass spectrometry and sample filtration conditions, the method exhibited satisfactory limits of detection (1 ng/L) and good filtration loss. The validated method was successfully applied to determine the concentrations of ET and ETA in wastewater samples (n = 245) from several wastewater treatment plants in China. The concentrations of the targets in positive samples ranged from less than the lower limits of quantitation to 47.71 ng/L. The method can meet ET monitoring and high-throughput analysis requirements.

Detection and quantification of etomidate and metomidate in human hairs by ultraperformance liquid chromatography with triple quadrupole mass spectrometry (UPLC-MS/MS).

PURPOSE: Intravenous narcotic agents, such as etomidate and metomidate, has been widely spread and abused in the world, including in Korea and China; thus, it is important to establish validated and sensitive analytical method for these compounds. Human hair as a biological sample has various advantages, including a wide detection window of drugs, compared to other typical samples, such as urine and blood in investigation. The purpose of this communication is to develop a reliable and useful method for the simultaneous detection and quantification of etomidate and metomidate in human hair samples by ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry (UPLC-MS/MS), and to apply it for authentic samples in abuse cases. METHODS: The hair samples were washed with a detergent solution, followed by with water and acetone. After drying, they were cut into approximately 2 mm sections and then ground to powder by a low-temperature grinder. The 20 mg of hair powder plus internal standard in 1 mL of methanol was vortexed and then centrifuged to obtain the supernatant layer, followed by subjecting to analysis. RESULTS: The coefficient of determination (r2) values of the calibration curves of etomidate and metomidate in the hair samples were both more than 0.99 in the range of 1-500 ng/mg and 1-500 pg/mg, respectively. The limits of detection and lower limits of quantification were 0.5 and 1 pg/mg, respectively, for the both target compounds. Other tested validation data were all satisfactory. Etomidate and metomidate could be detected in the all hair samples and cigarette oil, which were seized by the police. The concentrations of etomidate and metomidate obtained from 10 samples from suspects were 5.48-45.7 ng/mg and 3.60-377 pg/mg, respectively. The concentrations of etomidate and metomidate in the cigarette oil were 95.8 µg/mg and 2.8 µg/mg, respectively. CONCLUSIONS: In this study, a simple and reliable analytical method for etomidate and metomidate in the human hair has been established. To the best of our knowledge, this is the first report to establish a method for the simultaneous detection and quantification of etomidate and metomidate in the human hair, and to apply it to authentic samples seized in authentic cases.

Residual detection of buparvaquone, nystatin, and etomidate in animal-derived food products in a single chromatographic run using liquid chromatography-tandem mass spectrometry.

A reliable and highly sensitive screening method based on liquid chromatography coupled withtriple-quadrupoleelectrospray tandemmass spectrometry (LC-MS/MS) analysis has been developed for the detection and quantification of three veterinary drugs, including buparvaquone, nystatin, and etomidate impurity B CRS. The tested drugs were extracted from samples of porcine muscle, pasteurized whole milk, and eggs using 10mM ammonium formate in acetonitrile followed by liquid-liquid purification with n-hexane. Chromatographic separation was achieved on a Phenomenex Luna C18 analytical column using 0.1% formic acid in ultrapure water (A) and acetonitrile (B) as mobile phases. All the matrix-matched calibration curves were linear (R2≥0.9756) over the concentration levels of the drugs tested. Recovery at two spiking levels (equivalent to the limit of quantification (LOQ)=5ng/g and 2×LOQ) ranged from 72.88% to 92.59% with intra- and inter-day precisions <17%, except for porcine muscle spiked with 5ng/g nystatin (RSD=25.15%). Samples collected from markets located in Seoul, Republic of Korea, tested negative for all the drugs analyzed. In summary, this method is suitable for screening and quantifying the selected drugs in a single chromatographic run and with high selectivity in animal-derived food products meant for human consumption.

Synthesis of fused imidazoles, pyrroles, and indoles with a defined stereocenter α to nitrogen utilizing Mitsunobu alkylation followed by palladium-catalyzed cyclization.

Nitrogen-containing fused heterocycles comprise many compounds that demonstrate interesting biological activities. A new synthetic approach involving Mitsunobu alkylation of imidazoles, pyrroles, and indoles followed by palladium-catalyzed cyclization has been developed providing access to fused heterocycles with a defined stereochemistry α to nitrogen. While ethyl imidazole or indole carboxylates are good substrates for Mitsunobu alkylation with optically pure secondary benzylic alcohols, the corresponding pyrroles are poor substrates presumably due to the increased pK(a) of the NH. The presence of a synthetically versatile trichloroacetyl functional group on the pyrroles significantly reduces the pK(a) and thereby facilitates Mitsunobu alkylation. Subsequent cyclization of the alkylated products mediated by palladium in the presence or absence of a ligand gave fused heterocycles in good to excellent yields.

Development and validation of a robust capillary electrophoresis method for impurity profiling of etomidate including the determination of chiral purity using a dual cyclodextrin system.

An enantioselective CE assay for the simultaneous determination of the enantiomeric purity and of related substances of etomidate has been developed and validated using a binary chiral selector system employing 30 mg/mL beta-CD and 4.6 mg/mL sulfated-beta-CD in a 150 mM potassium phosphate buffer, pH 2.1. The method was validated with respect to specificity, range, linearity, LOQ and LOD, precision and accuracy. The assay allowed the detection and determination of related substances including (S)-etomidate at the 0.05% w/w level, the reporting threshold as defined by the International Conference on Harmonisation guidelines as well as the European Pharmacopoeia. Robustness testing was carried out by an "Augmented Plackett-Burman" design. Quantitation of the compounds was performed by calibration graphs with respect to lidocaine hydrochloride as internal standard and by peak area normalization, the procedure usually applied by pharmacopoeias. Although data obtained from the calibration graphs constructed with the aid of the internal standard were more accurate based on compound recovery, peak area normalization may also be used without significant loss of accuracy and precision.

The insulin pump as murder weapon: a case report.

Microprocessor-controlled insulin pumps designed for continuous delivery of short-acting insulin analogs into subcutaneous tissues offer several important potential benefits for diabetic patients. The delivery of other substances using these systems is technically feasible. We present a case of homicide involving lethal doses of etomidate and atracurium injected via the victim's insulin pump. This unique situation could be encountered by homicide investigators more frequently as the popularity of these systems continues to grow.

Gas chromatographic--mass spectrometric determination of etomidate in mouse brain.

A simple, rapid and reliable method was developed to determine the concentration of etomidate [ethyl-1-(1-phenylethyl)-1 H-imidazole-5-carboxylate] in mouse brain tissue by gas chromatography-mass spectrometry (GC-MS). Ethyl 5-amino-1-phenyl-4-pyrazolecarboxylate was used as internal standard (IS) and liquid-liquid extraction using ethyl ether as the solvent. The method demonstrated excellent recovery (93%) and a linear calibration range of 50-2500 ng/0.2 g. Intra-day accuracy and precision had an error and coefficient of variation of less than 8.7% and 4.2%, respectively. The limit of detection was 1 ng in mouse brain. Our results suggest that this new method is suitable for the quantitative analysis of etomidate in mouse brain tissue.

Tiopental sódico, etomidato y propofol: efectos sobre tensión arterial y frecuencia cardíaca durante la inducción anestésica / Thiopental sodium etamidat and propofol: effects on arterial pressure and heart rate during the anesthetic induction

Con el fin de comparar las variaciones de tensión arterial y frecuencia cardíaca durante la inducción anestésica con Tiopental Sódico, Etomidato y Propofol, se estudiaron 30 pacientes de edades comprendidas entre 25 y 50 años, ASA I, sin premedicación que iban a ser sometidos a anestesia general para cirugía electiva. Fueron distribuidos aleatoriamente en 3 grupos. En un grupo, la anestesia fue inducida con Tiopental Sódico (4 mg/kg), otro grupo con Etomidato (0,3 mg/Kg), y el otro con Propofol (2,5 mg/kg). Todos los pacientes recibieron Fentanil (5 mg/kg) 10 minutos antes de la inducción anestésica. La tensión arterial sistólica y diastólica disminuyó en los 3 grupos sin diferencias significativas. La frecuencia cardíaca descendió en los grupos inducidos con Propofol y con Etomidato. Las variaciones de la frecuencia cardíaca en los 3 grupos fueron significativas. Se concluyó que con la administración de Etomidato se produce más estabilidad hemodámica que con Tiopental Sódico o Propofol