[Source Apportionment of Morphine in Wastewater].

It is a new approach to identify legal or illegal use of morphine through information on municipal wastewater. However, the sources of morphine in wastewater are complex, and distinguishing the contribution of different sources has become a key issue. A total of 262 influent samples from 61 representative wastewater treatment plants in a typical city were collected from October 2022 to March 2023. The concentrations of morphine, codeine, thebaine, papaverine, noscapine, and monoacetylmorphine were analyzed in wastewater and poppy straws. Combined with the proportion of alkaloids in poppy straws, the source analysis of alkaloids in wastewater was analyzed using the ratio method and positive matrix factorization model (PMF). Only five alkaloids were detected in wastewater, and monoacetylmorphine, a metabolite of heroin, was not detected. The concentrations of morphine and codeine were significantly higher than those of noscapine, papaverine, and thebaine. By constructing the ratios of codeine/(morphine + codeine) and noscapine/(noscapine + codeine), the source of poppy straw could be qualitatively distinguished. The PMF results showed that three sources of morphine for medical use, poppy straw, and codeine contributed 44.9%, 43.7%, and 9.4%, respectively. The different sources varied in these months due to the COVID-19 and influenza A outbreaks, in which the use of drugs containing poppy straws and codeine was the main source, whereas the use of morphine analgesics remained relatively stable. Inventory analysis further demonstrated the reliability of the source contributions from the PMF model, and morphine was not abused in this city.

Toxicokinetics of thebaine in those consuming non-food grade poppy seeds as a tea.

INTRODUCTION: Thebaine is an alkaloid in poppy seeds that is neurotoxic to animals. Data on its clinical effects and toxicokinetics in people are minimal. In 2022, poppy seeds high in thebaine entered the Australian food market, and people consuming tea made from these poppy seeds developed poisoning. METHODS: Three patients who drank poppy seed tea and developed neuromuscular toxicity consented for thebaine to be quantitated in serial blood samples. Blood samples were analyzed by liquid chromatography with high-resolution mass spectrometry. RESULTS: Case 1: A man in his 60s presented with drowsiness, vomiting, malaise and myoclonus. He developed metabolic acidosis with hyperlactataemia, acute kidney injury requiring haemodialysis, convulsions, rhabdomyolysis, and was in the hospital for 18 days. The admission thebaine blood concentration was 2.1 mg/L, and the apparent elimination half-life was 14.8 h. Case 2: A man in his 30s presented with myoclonus, rigidity, vomiting, and dizziness. He developed metabolic acidosis with hyperlactataemia, acute kidney injury, and myalgias. The admission thebaine blood concentration was 4.1 mg/L, and the apparent elimination half-life was 11.6 h. Case 3: A man in his 30s presented with myoclonus, rigidity, clonus, diaphoresis, and abdominal pain. The admission thebaine blood concentration was 2.2 mg/L, and the apparent elimination half-life was 8.3 h. DISCUSSION: Neuromuscular toxicity, metabolic acidosis with hyperlactataemia, acute kidney injury, and gastrointestinal symptoms were prominent clinical features in these patients after drinking poppy seed tea. Effects persisted for days, and all survived, despite thebaine concentrations far exceeding those in published forensic reports, although human data are sparse. Compared to rats, the thebaine apparent elimination half-life is much longer in humans who develop symptoms at lower concentrations. CONCLUSIONS: Despite relatively high thebaine blood concentrations and moderate to severe poisoning, outcomes were favourable with early presentations. It is possible that acute kidney injury prolongs the apparent elimination half-life of thebaine.

A cluster of acute thebaine poisonings from non-food grade poppy seeds in the Australian food supply.

INTRODUCTION: Poppy seed tea is used for its opioid effects and contains multiple opium alkaloids, including morphine, codeine, papaverine, and thebaine. Animal studies indicate thebaine has strychnine-like properties, but there is limited literature describing human thebaine poisoning. We describe a cluster of acute thebaine poisoning in people ingesting tea made using poppy seeds with high thebaine content that entered the Australian food supply chain. METHODS: This is an observational study of patients poisoned after drinking poppy seed tea. Cases were identified by three prospective toxicovigilance systems: the Emerging Drug Network of Australia collaboration, the New South Wales Prescription, Recreational and Illicit Substance Evaluation program, and the Emerging Drugs Network of Australia Victoria study. We report characteristics of clinical toxicity in cases with reported ingestion of poppy seed tea and analytical confirmation of thebaine exposure. RESULTS: Forty cases presenting with multi-system toxicity following poppy seed tea ingestion were identified across seven Australian states/territories from November 2022 to January 2023. Blood testing in 23 cases confirmed high thebaine concentrations. All 23 were male (median age 35, range 16-71 years). All patients experienced muscle spasms. Rigidity was described in nine, convulsions in six, while rhabdomyolysis, acute kidney injury, and metabolic acidosis occurred in five patients. There were two cardiac arrests. The thebaine median admission blood concentration was 1.6 mg/L, with a range of 0.1-5.6 mg/L, and was the dominant opium alkaloid in all samples. Convulsions, acute kidney injury, metabolic acidosis, and cardiac arrest were associated with increasing median thebaine concentrations. Four patients were managed in the Intensive Care Unit, with two receiving continuous kidney replacement therapy (one also received intermittent haemodialysis) for kidney injury. There was one death. CONCLUSIONS: Thebaine toxicity, like strychnine poisoning, resulted in neuromuscular excitation characterized by muscle spasm, rigidity, and convulsions. Severe toxicity, including acute kidney injury, metabolic acidosis, and cardiac arrest, appears dose-dependent.

A Fatal Case Report Resulting from the Abuse of the Designer Benzodiazepines Clonazolam and Flualprazolam in Conjunction with Dried Opium Poppy Pods‡.

Toxicologists are often confronted with the abuse of multiple drugs and are obliged to decide which compound may have been the cause of death. We report on a 21-year-old man (182 cm, 84 kg), who was found unconscious in his bed. Beside him, the police found several controlled substances, among them were dried opium poppy pods containing thebaine, codeine and morphine, a clear liquid with the designer benzodiazepines flualprazolam and clonazolam and a white powder with the imprint SGT-25, instead of SGT-78 (CUMYL-4CN-BINACA). These compounds were also found in the urine sample following a non-targeted gas chromatography-mass spectrometry and a targeted liquid chromatography-tandem mass spectrometry (LC-MS-MS) screening approach. Subsequently, these compounds were quantified in whole femoral blood and scalp hair. Based on the concentrations measured in femoral blood in particular, we assume that the deceased had taken a lethal dose of the designer benzodiazepines-flualprazolam (0.74 mg/L) and clonazolam (2.08 mg/L), an extremely high dose of the opiates-thebaine (0.81 mg/L), codeine (0.23 mg/L) and morphine (0.13 mg/L ) and a high dose of the synthetic cannabinoid-CUMYL-4CN-BINACA (0.01 mg/L). Besides postmortem concentrations, we also present electron impact and electrospray ionization mass spectra of compounds found in the vicinity of the decedent, namely the tryptamines-4-hydroxy-N-isopropyl-N-methyltryptamine (4-HO-MIPT), 4-hydroxy-N-ethyl-N-methyltryptamine (4-HO-MET) and 4-acetoxy-N,N-diethyltryptamine (4-ACO-DET), the amphetamines-3-fluoroethamphetamine (3-FEA) and 2-fluoromethamphetamine (2-FMA) and the arylcyclohexylamines-N-ethyldeschloroketamine (O-PCE), 3-methoxyphencyclidine (3-MeO-PCP) and 3-methoxyeticyclidine (3-MeO-PCE).

Micronization of Thebaine Extracted from Papaver bracteatum Lindl. Using Supercritical Fluid Technology.

BACKGROUND: Thebaine, as a main opiate alkaloid extracted from Papaveraceae plants, is widely used in the synthesis of many pharmaceutical ingredients such as buprenorphine, naltrexone, naloxone, and hydrocodone. Nevertheless, thebaine and related derivatives are often insoluble in aqueous media and have low bioavailability in digestive systems. OBJECTIVE: Reducing particle size and changing the morphology can mitigate the mentioned problem. In this study, extraction of thebaine from the capsule, stem, and root of Papaver bracteatum L. was optimized and micronization of extract components was developed to study solubility. METHODS: The extraction process was performed using supercritical carbon dioxide. Experimental central composite design was employed to determine the optimal conditions. Analysis of extract was done using a validated high performance liquid chromatography method and mass spectrometry. The micronization process was performed using an inhouse developed supercritical technique. The nanoparticles were characterized using field emission scanning electron microscopy (FESEM) and ImageJ software. The effect of micronization was explored on the solubility of extract components via ultraviolet spectroscopy. RESULTS: The percentage of thebaine in dried capsule, stem, and root powder was about 1.05, 0.31, and 0.83% respectively. The extraction results indicate that supercritical pressure has the greatest effect on the extraction yield. Analysis of FESEM images revealed that nanoparticles of extract components with particle size distribution of 5-100 nm were collected successfully. CONCLUSION: The extraction results indicate that pressure has the greatest effect on the extraction yield. In vitro studies illustrated that the solubility of extract components increased up to 1.7 times during the micronization process. HIGHLIGHTS: Expansion of supercritical methods as an effective method was performed for extracting and preparing alkaloid nanoparticles. This process led to improved oral bioavailability of alkaloids.

Concentrations of the Opium Alkaloids Morphine, Codeine, and Thebaine in Poppy Seeds are Reduced after Thermal and Washing Treatments but are Not Affected when Incorporated in a Model Baked Product.

Limited information exists on the effectiveness of potential treatments to reduce levels of opium alkaloids that may be present in seeds from poppy (Papaver somniferum L.). Poppy seeds containing morphine at relatively lower (14.7 mg kg-1) and higher (210.0 mg kg-1) concentrations were subjected to dry heat and steam treatments, water washing, and baking. Sample extracts were then analyzed using liquid chromatography-tandem mass spectrometry for the opium alkaloids morphine, codeine, and thebaine. The results indicated that thermal treatment promoted opium alkaloid degradation in poppy seed samples, with a 50% loss of morphine observed after 30-40 min at 200 °C. Water washing reduced concentrations of opium alkaloids in poppy seeds by approximately 50-80%, while steam treatment resulted in reduction of morphine in only one sample type. Importantly, baking had no significant effect on concentrations of opium alkaloids. Overall, these results indicate that opium alkaloids may not be significantly affected by baking or steam application and that poppy seeds may require water washing or extended thermal treatment to promote reduction of these compounds.

Detection of opium alkaloids in a Cypriot base-ring juglet.

A method has been developed for extracting poppy alkaloids from oily matrices, specifically lipid residues associated with archaeological ceramics. The protocol has been applied to fresh and artificially aged poppyseed oil and to residue from a Late Bronze Age Cypriot juglet in the collections of the British Museum. The juglet is of a type that has been linked with ancient trade in opium due to its poppy-head shape and wide distribution; it is a rare example of an intact vessel with contents sealed inside. Bulk analysis of the residue by GC-EI-MS and pyGC-EI-MS indicated a degraded plant oil and possible presence of papaverine. Analysis of the alkaloid extracts by HPLC-ESI-MS using both triple quadrupole and FTICR mass spectrometers detected the five primary opium alkaloids in fresh poppyseed oil and papaverine in most of the aged samples. Papaverine and thebaine were detected in the juglet residue, providing the first rigorous chemical evidence to support a link between this vessel type and opium, or at least poppies. The association of opium with oil raises new questions about the ancient purpose of the commodities within these vessels, and the low levels (ng g-1) of opiates detected in this unusually well-preserved residue shed doubt on the scope for their detection in more fragmentary ceramic remains (potsherds). Papaverine was found to exhibit challenging carryover behaviour in all the analytical methods used in this study. The phenomenon has not been reported before and should be considered in future analyses of this analyte in all application areas.

Quantification of Morphine, Codeine, and Thebaine in Home-Brewed Poppy Seed Tea by LC-MS/MS.

Recently, medical examiners reported two cases of a 21-year-old male and 24-year-old male with high amounts of morphine in their blood at autopsy. It was suspected that the decedents ingested lethal amounts of morphine from home-brewed poppy seed tea. No studies to date have investigated opium alkaloid content extracted from poppy seeds by home-brewing methods. Various poppy seed products were purchased from online sources and extracted with four home-brewing methods representative of recipes found on drug user forums. Morphine, codeine, and thebaine were quantified in the tea extracts by liquid chromatography-tandem mass spectrometry using a validated analytical method. Morphine, codeine, and thebaine concentrations from seeds were <1-2788 mg/kg, <1-247.6 mg/kg, and <1-124 mg/kg, respectively. Alkaloid yield varied between extractions, but regardless of extraction conditions, lethal amounts of morphine can be rinsed from poppy seed coats by home-brewing methods.

Evaluation of hydrophilic interaction liquid chromatography stationary phases for analysis of opium alkaloids.

The separation of a mixture containing five major opium alkaloids, namely morphine, codeine, thebaine, noscapine and papaverine has been investigated in hydrophilic interaction liquid chromatography (HILIC) mode using five different stationary phases: bare silica, zwitterion, aminopropyl, diol and cyanopropyl. In order to propose the appropriate column for separation and purification, retention behaviors of the five natural opioids have been studied on mentioned HILIC stationary phases. The mechanism of separation in diverse HILIC media, based on the formation of water-rich layer on surface of the HILIC stationary phases and the physicochemical properties of opium alkaloids, such as pKa (acidic pK) and the octanol-water distribution coefficient (log Do/w) are discussed. Chromatographic responses including modified limit of detection LODm, signal to noise ratio (S/N)m, and defined modified RSm have considered for suggestion of the suitable column for quantitative/qualitative and preparative purposes. According to the obtained results, diol stationary phase is best suited for analytical chromatography, whereas bare silica and zwitterionic stationary phases are appropriate for preparative applications.

Rapid identification of a narcotic plant Papaver bracteatum using flow cytometry.

In May 2011, numerous poppy plants closely resembling Papaver bracteatum Lindl., a type of narcotic plant that is illegal in Japan, were distributed directly from several large flower shops or through online shopping throughout Japan, including the Tokyo Metropolitan area. In order to better identify the narcotic plants, the relative nuclear DNA content at the vegetative stage was measured by flow cytometric (FCM) analysis in 3 closely-related species of the genus Papaver section Oxytona, namely P. orientale, P. pseudo-orientale, and P. bracteatum, based on the difference between the chromosome numbers of these species. The results showed that the nuclear DNA content differed between these 3 species, and that most of the commercially distributed plants examined in this study could be identified as P. bracteatum. The remaining plants were P. pseudo-orientale, a non-narcotic plant. In addition, the FCM results for the identification of P. bracteatum completely agreed with the results obtained by the morphological analysis, the inter-genic spacer sequence of rpl16-rpl14 (PS-ID sequence) of chloroplast DNA, and the presence of thebaine. These results clearly indicate the usefulness of FCM analysis for the identification of P. bracteatum plants, including when they are in their vegetative stage.

The poppy seed defense: a novel solution.

A major toxicological challenge is distinguishing whether morphine in urine, in the absence of 6-monoacetylmorphine (6-MAM), originates from 'street' heroin use or poppy seed ingestion. Manufacturing byproducts from the synthesis of illicit heroin include those that originate from the reaction of acetic anhydride with the alkaloid impurity, thebaine, which undergoes skeletal rearrangement, resulting in compounds with a 2-(N-methylacetamido)ethyl side-chain. The hypothesis that the tertiary amide in this side-chain is resistant to endogenous hydrolysis was supported from in-vitro experiments; a glucuronide metabolite (designated 'ATM4G') was identified that may be used as a marker of 'street' heroin administration. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for this metabolite was then performed on selected urine specimens from 22 known heroin users, these being negative on routine testing for 6-MAM by gas chromatography-mass spectrometry (GC-MS), using the generally applied reporting threshold of 10 ng/mL, but positive for the presence of morphine. Peaks corresponding to the retention time for the metabolite marker were clearly observed for 16 of the 22 samples, with variations of the ratios of its three dependent ions being within ± 30% of that produced in vitro. Conversely, 6-MAM was detected in only 3 samples, but at concentrations <1 ng/mL. Such a high frequency for the presence of the metabolite marker in urine, in the absence of 6-MAM, is noteworthy and suggests that detection of this metabolite may offer an important advance in forensic toxicology, allowing the development of a new and more definitive test for heroin abuse and thus a potential solution to the so-called 'poppy seed defense'.

Analysis of fluid extracts obtained from Papaver rhoeas petals contaminated with Papaver bracteatum petals.

In this paper, we report a case of misidentification of medicinal plants involving dried petals of Papaver rhoeas (red poppy) contaminated with Papaver bracteatum (scarlet poppy) petals. Preliminary TLC analysis indicated the presence of thebaine either in the fluid extracts or in the petals. It was therefore necessary to carry out an accurate botanic examination of the plant material, which revealed contamination of the red poppy petals with scarlet poppy petals. Moreover, to confirm the adulteration, we developed and validated an efficient, reversed-phase ion pair HPLC method for determination of the alkaloids specific for the Papaver species. Six petal batches and five commercial fluid extracts were analyzed. Only one petal batch from Iran contained thebaine and its analogue oripavine while the alkaloids typical for the Papaver bracteatum species were identified in all fluid extracts, meaning that they were all prepared with contaminated petals.

Exposure of consumers to morphine from poppy seeds in Hungary.

Poppy seed-containing foods are popular dishes in Hungary and some other Central European countries. The alkaloids of poppy are used in the production of medicines. Poppy seeds used as food may also contain considerable amounts of alkaloids, which raises the question of food safety. Morphine, codeine, thebaine and noscapine concentrations of poppy seed samples from the period 2001-2010 and consumption data from two Hungarian surveys, carried out in 2003 and 2009, were evaluated. Exposure calculations were made for morphine intake by both point estimate and probabilistic methods, and the uncertainty of the calculated values was estimated. The point estimate for the acute consumer exposure, calculated using the 97.5th percentiles of morphine concentration and of poppy seed consumption and taking into account the reduction of morphine content by processing, was 78.64 µg (kg bw)⁻¹ day⁻¹ for adults, and 116.90 µg (kg bw)⁻¹ day⁻¹ for children. Based on probabilistic estimations, the 97.5th and 99th percentile exposures ranged between 18.3-25.4 and 25.6-47.4 µg (kg bw)⁻¹ day⁻¹ for adults, and between 32.9 and 66.4 µg (kg bw)⁻¹ day⁻¹ for children, respectively. As a no observed effect level (NOEL) had not been established, the significance of exposure could not be assessed.

Determination of thebaine in water samples, biological fluids, poppy capsule, and narcotic drugs, using electromembrane extraction followed by high-performance liquid chromatography analysis.

Opium determination is of great importance from toxicological and pharmaceutical standpoints. In present work, electromembrane extraction (EME) coupled with high-performance liquid chromatography (HPLC) and ultraviolet (UV) detection was developed for determination of thebaine as a natural alkaloid, in different matrices containing water, urine, poppy capsule, street heroine, and codeine tablet. Thebaine migrated from 3 mL of sample solutions, through a thin layer of 2-nitrophenyl octyl ether (NPOE) immobilized in the pores of a porous hollow fiber, and into a 15 µL acidic aqueous acceptor solution present inside the lumen of the fiber. The variables of interest, such as chemical composition of the organic liquid membrane, stirring speed, extraction time and voltage, pH of donor and acceptor phases and salt effect in the EME process were optimized. Under optimal conditions, thebaine was effectively extracted from different matrices with recoveries in the range of 45-55%, which corresponded to preconcentration factors in the range of 90-110. Good linearity was achieved for calibration curves with a coefficient of estimation higher than 0.997. Detection limits and intra-day precision (n=3) were less than 15 µg L(-1) and 8.9%, respectively.

Thebaine in hair as a marker for chronic use of illegal opium poppy substances.

Opium poppy products are often illegally used for both recreational and medicinal purposes. In order to demonstrate the ingestion of opium poppy substances, morphine, codeine and their metabolites have been identified. However, morphine and codeine also originate from the ingestion of therapeutic drugs. Therefore, thebaine, one of the main opium alkaloids, in hair was suggested as a marker for chronic use of illegal opium poppy substances in the present study. First, thebaine was included in the analyte list of our routine analytical method for the simultaneous quantification of codeine, morphine, norcodeine, normorphine and 6-acetylmorphine (6-AM) in hair, which was fully validated previously. Then, the incorporation of thebaine and other opiates into hair and the effect of hair pigmentation were examined using lean Zucker rats with both dark grey and white hair on the same body. Thebaine was also measured in hair samples from actual cases of opium poppy substance use. Consequently, thebaine in hair was demonstrated as a marker of chronic use of illegal opium poppy substances using an animal study and actual cases. Thebaine and other opiates were successfully measured in pigmented hair from rats that ingested raw opium suspension. Moreover, thebaine identified in hair excluded possibility of ingestion of pharmaceutical opiates in actual cases.

Optimized ultrasound-assisted extraction procedure for the analysis of opium alkaloids in papaver plants by cyclodextrin-modified capillary electrophoresis.

This study investigated the use of ultrasound-assisted extraction to improve the extraction efficiency of morphine, codeine and thebaine from the papaver plants. Extraction conditions such as type of solvent, temperature, duration, frequency and power level of ultrasonic were optimized and the influences of different parameters on resolution of alkaloids in CE were studied. The optimized condition for CE separation includes a sodium phosphate buffer (100 mM, pH 3.0) containing 5 mM alpha-CD. The optimized extraction conditions for ultrasound-assisted extraction was an extraction time of 1 h, an ultrasonic frequency of 60 kHz with water-methanol (80:20) at 40 degrees C as the extraction solvent. The LOD for alkaloids was found to be 0.1 microg/mL at a signal-to-noise ratio of 3:1. The RSDs for peak areas were in the range of 1.4-4.4%. The amounts of opium alkaloids (mg/100 g dried sample) in four Iranian papaver plants were found to be in the range of 7.8-8.7 (morphine), 5.5-9.5 (codeine) and 1.4-10.4 (thebaine). It should be emphasized that no cleanup of the filtered extract was required; hence, direct determination after extraction drastically simplifies the analytical process.

Simultaneous chemiluminescence determination of thebaine and noscapine using support vector machine regression.

In this work, a batch chemiluminescence (CL) method has been proposed for the simultaneous determination of two structurally similar alkaloids, noscapine and thebaine. The method is based on the kinetic distinction of the CL reactions of noscapine and thebaine with Ru(bipy)(3)(2+) and Ce(IV) system in a sulfuric acid medium. The least squared support vector machine (LS-SVM) regression was applied for relating the concentrations of both compounds to their CL profiles. The parameters of the model consisting of sigma(2) and gamma were optimized by constructing LS-SVM models with all possible combinations of these two parameters to select the model with the minimum root mean squared error of cross validation (RMSECV) as the best. The parameters of this model were then selected as optimized values. Under the optimized experimental conditions for both compounds, the detection limits obtained using the LS-SVM regression were 0.08 and 0.1 micromo lL(-1) for noscapine and thebaine, respectively. The proposed method was utilized for the simultaneous determination of the compounds in pharmaceutical formulations and plasma samples with satisfactory results.

Separation and determination of five major opium alkaloids with mixed mode of hydrophilic/cation-exchange monolith by pressurized capillary electrochromatography.

A method for the separation and determination of five major opium alkaloids (narcotine, papaverine, thebaine, codeine, and morphine) in pericarpium papaveris by pressurized CEC (pCEC) with monolithic column has been developed. Under the optimum condition, linear calibration ranges of narcotine, papaverine, thebaine, codeine, and morphine were obtained as 2-85, 2-85, 5-75, 10-65, and 10-65 microg/mL, respectively. LODs of these analytes were 1.5-6.0 microg/mL. The RSD (n=7) of the migration time and peak area were 1.94-5.24 and 4.05-8.21%, respectively. The proposed method was successfully applied to the analysis of pericarpium papaveris samples. Average recoveries of 79.0-95.9% at different fortified levels of alkaloids were achieved with RSD less than 4.6%. Meanwhile, the mechanism of the separation of the alkaloids on the monolithic column was also discussed. The result showed that the separation of alkaloids was mainly based on the mixed mode of hydrophilic interaction (HI) and cation exchange.

Determination of opiate alkaloids in process liquors using capillary electrophoresis.

This paper describes the determination of opiate alkaloids (morphine, codeine, oripavine and thebaine) in industrial process liquors using capillary zone electrophoresis with UV-absorption detection at 214 nm. A study of cyclodextrin type and concentration revealed that the addition of 30 mM hydroxypropyl-beta-cyclodextrin to the electrolyte solution (100mM Tris adjusted to pH 2.8) was suitable to resolve the four analytes of interest. Typical analysis time was 12 min and the limit of detection for each alkaloid was 2.5 x 10(-6) M. The results for the proposed methodology were in good agreement with those of a conventional HPLC procedure. Under the same conditions, short-end injection was used to reduce the effective separation length from 41.5 to 8.5 cm, which allowed the determination of morphine and thebaine in process liquors within 2.5 min.

Simultaneous analysis of thebaine, 6-MAM and six abused opiates in postmortem fluids and tissues using Zymark automated solid-phase extraction and gas chromatography-mass spectrometry.

Opiates are some of the most widely prescribed drugs in America and are often abused. Demonstrating the presence or absence of opiate compounds in postmortem fluids and/or tissues derived from fatal civil aviation accidents can have serious legal consequences and may help determine the cause of impairment and/or death. However, the consumption of poppy seed products can result in a positive opiate drug test. We have developed a simple method for the simultaneous determination of eight opiate compounds from one extraction. These compounds are hydrocodone, dihydrocodeine, codeine, oxycodone, hydromorphone, 6-monoacetylmorphine, morphine, and thebaine. The inclusion of thebaine is notable as it is an indicator of poppy seed consumption and may help explain morphine/codeine positives in cases where no opiate use was indicated. This method incorporates a Zymark RapidTracetrade mark automated solid-phase extraction system, gas chromatography/mass spectrometry, and trimethyl silane (TMS) and oxime-TMS derivatives. The limits of detection ranged from 0.78 to 12.5 ng/mL. The linear dynamic range for most analytes was 6.25-1600 ng/mL. The extraction efficiencies ranged from 70 to 103%. We applied this method to eight separate aviation fatalities where opiate compounds had previously been detected.