Opium Alkaloids Research Articles

Fast and green methodology based on miniaturised liquid–liquid extraction with a hydrophobic natural deep eutectic solvent of opium alkaloids from poppy seed beverages

Currently, the development of environmentally friendly analytical methodologies is a challenge for analytical chemistry. Therefore, the search for solvents to extract analytes of interest from complex matrices has progressed considerably in recent years. In the present work, 15 hydrophobic natural deep eutectic solvents (HNADES) consisting of a mixture of different donors and acceptors in different ratios have been prepared and compared to evaluate the most efficient extraction of opium alkaloids (OA) from fortified water samples. After selecting the most effective one consisting in a mixture of thymol and camphor in the ratio 1:1 ([Thy]:[Cam] 1:1), a rapid analytical methodology to determine OA in poppy seed beverages was optimised and validated for the first time. It was based on a miniaturised liquid–liquid extraction (m-LLE) with 0.5 mL of sample and 0.5 mL of HNADES by vortexing for 1 min, followed by 1 min centrifugation and subsequent analysis by high-performance liquid chromatography with diode array detector (HPLC-DAD). The validation was successful, showing extraction efficiencies between 91 and 107 % for all analytes, low limits of quantification (0.1 µg/mL for all analytes, except for morphine, 0.4 µg/mL) and precision values below 15 %. In addition, the greenness of the method was evaluated, obtaining a 0.79 on the AGREEprep metric scale. Therefore, it was demonstrated that the methodology developed to analyse OAs in poppy seed beverage was efficient, fast, simple and environmentally friendly.

Signal detection of drugs associated with obstructive and central sleep apnoea

We aim to discover new safety signals of drug-induced sleep apnoea (SA), a global health problem affecting approximately 1 billion people worldwide.We first conducted a series of sequence symmetry analyses (SSA) in a cohort composed from all patients who received a first SA diagnosis or treatment between 2006 and 2018 in the Echantillon Généraliste des Bénéficaires (EGB), a random sample of the French healthcare database. We used two primary outcomes to estimate the sequence ratio (SR) for all drug classes available in France: a sensitive one (diagnosis or treatment of SA) and a specific one (Positive Airway Pressure (PAP) therapy). We then performed disproportionality analyses using the “Bayesian neural network method” on all cases of sleep apnoea (MedDRA high level term) reported up to November 2023 in the World Health Organisation (WHO) pharmacovigilance database.Among the 728,167 individuals, 46,193 had an incident diagnosis or treatment for SA and 17,080 had started an incident treatment by PAP therapy. Fifty-eight drug classes had a significant SR, with 7 considered highly plausible: opium alkaloids and derivatives, benzodiazepine derivatives, other centrally acting agents, other anxiolytics, carbamic acid esters, quinine and derivatives and antivertigo preparations; with consistent signals found for the first 3 drug classes in the disproportionality analysis.In this signal detection study, we found that opioids, benzodiazepines (but not Z-drugs) and myorelaxing agents are associated with the onset or aggravation of SA. Moreover, a new safety signal for antivertigo preparations such as betahistine emerged and needs to be further explored.

Concise Total Synthesis of (-)-Codeine.

Codeine and morphine are among the few natural products that are used directly as drugs for medical treatment. However, the availability of these is widely dependent on natural resources. Herein, we report an efficient enantioselective seven-step synthesis of (-)-codeine starting from simpler starting materials. The key steps involve microwave-assisted intramolecular cascade double heck cyclization to access the ABCE ring of opium alkaloids with the required stereocenters in one pot. A photoinduced intramolecular hydroamination of carboxamide forms the D ring and completes the pentacyclic core of the morphinans. Following that, an oxidation followed by global reduction leads to the formation of (-)-codeine. Our synthesis relies on simple and classical reactions to address the opium alkaloids and will serve as an efficient route to access the other morphinans.

Determination of Opium Alkaloid Content in Poppy Seeds Using Liquid Chromatography Coupled with a Mass Spectrometer with a Time-of-Flight Analyzer (UPLC-TOF-HRMS).

Opium poppy is a plant used in both the pharmaceutical and food industries. Substances found on the surface of dry poppy seeds belong to the group of opium alkaloids. However, the presence of these substances in food products poses a risk to consumer health, which is why new permissible levels for both substances in poppy seeds and derivative products have been introduced in Regulation (EU) 2023/915. This research aimed to analyze the content of all six opium alkaloids in poppy seeds provided directly by producers as well as those available on the local market in Poland. The research confirmed the presence of morphine in all examined poppy seed samples. The alkaloid content ranged from 12.46 to 102.86 mg/kg for seeds purchased in local markets and from 1.1 to 110.1 mg/kg for seeds obtained directly from producers. Both groups showed similar levels of morphine content as well as other OAs, which significantly exceeded the permissible limit of 20 mg/kg set by the European Commission (EU) 2023/915. These results indicate that the presence of morphine and other opium alkaloids in poppy seeds exceeds permissible levels, posing a serious health issue and necessitating further research and improvement in processing methods.

Improving the food safety of bakery products by simultaneously monitoring the occurrence of pyrrolizidine, tropane and opium alkaloids

The exponential number of food alerts about concerning levels of some plant-alkaloids, such as pyrrolizidine, tropane and opium alkaloids, have stressed the need to monitor their occurrence in foods to avoid toxic health effects derived from their intake. Therefore, analytical strategies to simultaneously monitor the occurrence of these alkaloids should be developed to ensure food safety an comply with regulations. Accordingly, this work proposes an efficient multicomponent analytical strategy for the simultaneous extraction of these alkaloids from commercial bakery products. The analytical method was validated and applied to the analysis of 15 samples, revealing that 100% of them contained at least one of the target alkaloids, in some cases exceeding the maximum limits legislated. Moreover, in two samples the 3 different alkaloid families were detected. These results confirm the importance of simultaneously monitoring these alkaloids in food and highlight also considering some opium alkaloids in current legislation.

Genomic and Cell-Specific Regulation of Benzylisoquinoline Alkaloid Biosynthesis in Opium Poppy.

Opium poppy is a crop of great commercial value as a source of several opium alkaloids for the pharmaceutical industries including morphine, codeine, thebaine, noscapine and papaverine. Most enzymes involved in benzylisoquinoline alkaloids (BIAs) biosynthesis in opium poppy have been functionally characterized, and opium poppy currently serves as a model system to study BIA metabolism in plants. BIA biosynthesis in opium poppy involves two biosynthetic gene clusters associated respectively with the morphine and noscapine branches. Recent reports have shown that genes in the same cluster are co-expressed, suggesting they might also be co-regulated. However, the transcriptional regulation of opium poppy BIA biosynthesis is not well studied. Opium poppy BIA biosynthesis involves three cell types associated with the phloem system: companion cells, sieve elements and laticifers. The transcripts and enzymes associated with BIA biosynthesis are distributed across cell types, requiring the translocation of key enzymes and pathway intermediates between cell types. Together, these suggest that the regulation of BIA biosynthesis in opium poppy is multilayered and complex, involving biochemical, genomic, and physiological mechanisms. In this review, we highlight recent advances in genome sequencing and single cell and spatial transcriptomics with a focus on how these efforts can improve our understanding of the genomic and cell-specific regulation of BIA biosynthesis. Such knowledge is vital for opium poppy genetic improvement and metabolic engineering efforts targeting the modulation of alkaloid yield and composition.

Panoramic chemical imaging of opium alkaloids in Papaver somniferum by TOF-SIMS

Accurate mapping of opium alkaloids in Papaver somniferum (P. somniferum) is significant for comprehensively elucidating their biosynthetic pathways and metabolic regulations. Here we describe a panoramic chemical imaging strategy based on time-of-flight secondary ion mass spectrometry (TOF-SIMS) that enables a thorough and precise visualization of the spatial differentiation of five opium alkaloids (morphine, codeine, thebaine, papaverine and noscapine) in P. somniferum. Notably, the opium alkaloids exhibited enrichment in the capsule, pistil, receptacle and peduncle. Moreover, a series of cross sections of a capsule were imaged to reveal a three-dimensional horizon of internal distribution of opium alkaloids. Opium alkaloids were observed enriched within the pseudoseptum and the “tube-like” structure of the inner pod wall, witnessing a downward trend toward the stigmatic disk. Finally, in high spatial resolution mode of TOF-SIMS, direct single-cell level chemical mapping of opium alkaloids in the phloem of the vascular bundles of P. somniferum receptacle was achieved for the first time. The introduced imaging strategy can provide multi-dimensional insights into the spatial distribution of opium alkaloids in P. somniferum, and the findings are expected to facilitate shedding light on the biological activities of these pharmacologically valued alkaloids.

Investigating the effect of different grinding conditions and methods on the concentration of opium alkaloids in poppy seeds as a good reduction practice

In recent years, following intoxications and false positive drug tests for poppy seeds, dangerously high concentrations of opium alkaloids (OAs) have been found. For this reason, health authorities are demanding studies to establish effective practices to reduce OAs in these seeds. Grinding, a common culinary process for various recipes, has previously been associated with potential morphine degradation. However, these studies have not established effective grinding conditions to decrease the concentration of all main OAs. Furthermore, due to the large variation in OAs concentration that can occur even in the same bag, this can be a difficult task. In view of the above, this study aimed to evaluate for the first time the impact of different grinding types, varying grinding time or repetitions, to determine any degradation trends of the main OAs present in poppy seeds. As a result, it was obtained a notable 20% degradation of morphine in the second grinding with grinders where the oil content of the seeds is not released, hinting at oil’s protective role against morphine oxidation. Therefore, the choice of grinding method is crucial. However, while acknowledging this, relying solely on this method as a good practice for OAs reduction may be insufficient, as it seems to have minimal impact on other OAs with any of the tested methods and conditions.

Design and Optimisation of Sustainable Sample Treatments Based on Ultrasound-Assisted Extraction and Strong Cation-Exchange Purification with Functionalised SBA-15 for Opium Alkaloids in Ground Poppy Seeds.

An analysis methodology was optimised and validated for the quantification of opium alkaloids (OAs) in ground poppy seeds. This involved ultrasound-assisted extraction (UAE) and solid-phase extraction (SPE) purification before analysis using a high-performance liquid chromatography mass spectrometry detector (HPLC-MS/MS). UAE was optimised through the design of experiments with three factors and a three-level full factorial design. For SPE optimisation, a commercial material was compared with a previously synthesised material of SBA-15 silica functionalised with sulfonic groups (SBA-15-SO3-). The synthesised material demonstrated superior efficiency with only 25 mg and proved to be reusable for up to four cycles. The methodology was properly validated in terms of linearity, limits of detection and quantification, and selectivity. Matrix effects were negligible; adequate recovery values (85-100%) and inter-day and intra-day precision (≤15%) were obtained. The greenness of the method was evaluated with the AGREEprep metric scale, being more environmentally friendly compared to OA analysis methods. Finally, the method was applied to different samples of ground poppy seeds and revealed a concentration of 140 mg/kg of morphine equivalents in one of the samples, surpassing the legislatively established limits by sevenfold. This highlights the need to analyse these types of samples to mitigate potential public health issues.

Functionalized carbon nanotube-polyaniline composite coating for on-line microextraction on a screw coupled with high performance liquid chromatography to determine opium alkaloids.

Anovel and efficient on-line microextraction on a screw coupled with high-performance liquid chromatography with an ultraviolet-visible detector was developed to extract and determine trace quantities of five opium alkaloids. All detections of the analytes were achieved at 210 nm. The surface of the screw grooves was electrochemically coated with the carbon nanotubes-COOH/polyaniline composite. The surface characterization was assessed by Fourier transform infrared spectroscopy and field emission scanning electron microscopy. The prepared screw was inserted into a cartridge of a guard column, and then the constructed microextraction on a screw device was placed in the loop of a six-port HPLC injection valve. The parameters affecting the extraction efficiency of the analytes were optimized using the one variable-at-a-time method. The effective parameters for the extraction efficiency of the analytes, including sample volume, extraction time, sampling flow rate, desorption solvent type, ionic strength, and pH were investigated and optimized. Under optimal conditions, the detection limits were 3-10 μg L-1, and the linear dynamic ranges were 10-2000 μg L-1 with a coefficient of determination greater than 0.9940. The inter-day and intra-day (n = 3) relative standard deviations were less than 7% and 5%, respectively. The proposed method was simple and reproducible, with an acceptable relative recovery (90-108%) for determining opium alkaloids in water and urine samples.

Possible Protective Effect of Low Dose of Papaverine on ANIT Induce Cholestasis in Rat

Abstract
 Intrahepatic cholestasis is clinical syndrome which cause either by defect in synthesis or bile acid flow, the pathophysiology of cholestasis is complicated by a number of variables, including oxidative stress, inflammatory response, and dysregulation of bile acid transporter . Rats, mice, and guinea pigs were utilized as experimental animals, and ANIT was administered to them in order to create a model that closely resembled intrahepatic cholestasis in human. This study examined the protective effects of papaverine, a non-narcotic opium alkaloid derived from papaver somniferum and discovered as an FXR agonist, on cholestasis in rats induced by alpha-naphthylisothiocyanate (ANIT). Rats utilized in this study divided into 3 groups (10 rats per each groups), group I (control) or vehicle group rat administered corn oil (1ml/kg) once daily 48 hour before sacrifice group II rats orally administered alpha-naphthylisothiocyanate (ANIT) 100mg/kg single dose 48hour before sacrifice group III rats administered 100mg/kg papaverine orally for 7 consecutive days and at day 5 rat administered alpha-naphthylisothiocyanate (ANIT) The results showed that papaverine treatment decreased alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, total bile acid, as well as increased antioxidant enzyme GPX and decreased MDA and inflammatory mediators tumor necrosis factor TNF- and interleukin IL1-β. In conclusion, papaverine may have a protective effect to alleviate ANIT-induced cholestasis and may be a therapeutic target to treat cholestasis.

Papaverine Enhances the Oncolytic Effects of Newcastle Disease Virus on Breast Cancer In Vitro and In Vivo.

Breast cancer is a lethal disease in females worldwide and needs effective treatment. Targeting cancer cells with selective and safe treatment seems like the best choice, as most chemotherapeutic drugs act unselectively. Papaverine showed promising antitumor activity with a high safety profile and increased blood flow through vasodilation. At the same time, it was widely noticed that virotherapy using the Newcastle disease virus proved to be safe and selective against a broad range of cancer cells. Furthermore, combination therapy is favorable, as it attacks cancer cells with multiple mechanisms and enhances virus entrance into the tumor mass, overcoming cancer cells' resistance to therapy. Therefore, we aimed at assessing the novel combination of the AMHA1 strain of Newcastle disease virus (NDV) and nonnarcotic opium alkaloid (papaverine) against breast cancer models in vitro and in vivo. Methods. In vitro experiments used two human breast cancer cell lines and one normal cell line and were treated with NDV, papaverine, and a combination. The study included a cell viability MTT assay, morphological analysis, and apoptosis detection. Animal experiments used the AN3 mouse mammary adenocarcinoma tumor model. Evaluation of the antitumor activity included growth inhibition measurement; the immunohistochemistry assay measured caspase protein expression. Finally, a semiquantitative microarray assay was used to screen changes in apoptotic proteins. In vitro, results showed that the combination therapy induces synergistic cytotoxicity and apoptosis against cancer cells with a negligible cytotoxic effect on normal cells. In vivo, combination treatment induced a significant antitumor effect with an obvious regression in tumor size and a remarkable and significant expression of caspase-3, caspase-8, and caspase-9 compared to monotherapies. Microarray analysis shows higher apoptosis protein levels in the combination therapy group. In conclusion, this study demonstrated the role of papaverine in enhancing the antitumor activity of NDV, suggesting a promising strategy for breast cancer therapy through nonchemotherapeutic drugs.

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.

Категоричний негативний висновок в експертизі наркотичних засобів

The article examines the rationale for an expert's categorical negative opinion on the example of an expert study of narcotic drugs from the poppy plant. The plant mass submitted for examination, which by its external features resembles poppy straw, was examined by microscopic and chemical methods. The microscopic examination revealed anatomical and morphological elements characteristic of poppy sleeping pills, which is the basis for classifying the substance under investigation as poppy straw. According to the List of Narcotic Drugs, Psychotropic Substances and Precursors, poppy straw containing narcotically active opium alkaloids is a narcotic drug. To confirm the presence of narcotically active opium alkaloids in poppy straw, the study was carried out by microscopic and thin-layer chromatography. As a result of the study, it was established that the poppy straw provided for the study did not contain any narcotically active opium alkaloids, and, therefore, was not a narcotic drug. The absence of opium alkaloids can be explained by the multiple extraction of poppy straw, as evidenced by its appearance, colour and smell of the solvent. The study of the residues of a dark brown substance from the surface of the dishes was carried out by thin-layer chromatography according to the standard method. As a result of the study, trace amounts of morphine, which is a narcotic drug, were found. The results of the study provided a categorical negative conclusion, which may be the basis for closing the criminal proceedings. The presence of a small amount of morphine in the substance on the surface of the dishes does not significantly affect this decision. Key words: categorical negative conclusion, forensic examination of narcotic drugs,narcotic drug, poppy straw, anatomical and morphological elements of poppy, opium alkaloids, extraction of poppy straw, microscopic method, thin-layer chromatography method.

Influence of fermentation and storage on the content of opium alkaloids in poppy seed yoghurt

There is a current trend to make yoghurts with seeds such as poppy seeds to enhance their nutritional benefits. These seeds may be contaminated with opium alkaloids (OAs) present in the own latex of the plant (Papaver somniferum L.). Food processing such as heat treatment, grinding or washing may reduce them, but lactic fermentation has not been studied. In this work, an analytical methodology was optimised based on a solid-liquid extraction (SLE) with water, a purification by magnetic solid-phase extraction (MSPE) with a mesostructured silica magnetic composite with β-cyclodextrin (Fe3O4 @SiO2 @mSiO2 @β-CD) and subsequent analysis by liquid chromatography coupled to a tandem mass detector (HPLC-MS/MS). The methodology was successfully validated in terms of linearity, limits of detection and quantification, matrix effect, precision, recovery tests, and selectivity. Therefore, it was applied to determine OAs in commercial yoghurts, detecting morphine, papaverine and noscapine in all of them but below the limit of quantification. Besides, the effect of fermentation was studied (6 and 18 h) and storage (1 week/ 4ºC), showing a considerable degradation effect (33–80%) in the first hours.

Unearthed opium: development of a UHPLC-MS/MS method for the determination of Papaver somniferum alkaloids in Daunian vessels.

Introduction: The analysis of organic residue in ancient vessels to investigate early-age civilization habits is an important archeological application that needs advanced analytical methods. However, these procedures should meet inherent requisites such as low sampling invasiveness and high sensitivity for trace analysis. This study deals with the development of advanced analytical methods for the detection of opium alkaloids in ceramic vessels and its first application to the study of Daunian pots dating back to the VIII-IV sec BC. Methods: All the stages of the analytical procedure, from sampling to analysis, were carefully optimized. Concerning sampling, the traditional scraping approach was compared with a swabbing strategy which permitted minimizing sample encroachment. Extraction was based on pressurized liquid extraction or ultrasound-assisted liquid extraction, followed by dispersive liquid-liquid microextraction, which allowed concentration enrichment. On the other hand, a UHPLC-MS/MS method was specifically developed and validated to obtain reliable data. Some Daunian pots, belonging to the Ceci-Macrini private archeological collection, were selected for sample withdrawal as their iconography could suggest opium usage. Results: Several of the analyzed samples resulted positive to thebaine and less frequently to morphine and codeine; furthermore, 70% of the analyzed items tested positive for at least one opium alkaloid. Positive findings were common to all the samples collected in the pots, suggesting that scraping and swabbing provided comparable results and validating this unusual sampling strategy. All samples were additionally analyzed by UHPLC-HRMS to further improve the confidence level of the identified compounds. The obtained results shed new light on the hypothesis of opium usage by the ancient Daunian civilization. Furthermore, this study provided suitable analytical tools for further investigations on the same topic, with a good level of confidence in the quality of the results.

Opium alkaloids, biosynthesis, pharmacology and association with cancer occurrence

Papaver somniferum L. (Family: Papaveraceae) is a species well known for its diverse alkaloids (100 different benzylisoquinoline alkaloids (BIAs)). L-tyrosine serves as a precursor of several specific metabolites like BIAs. It has been used as an antitussive and potent analgesic to alleviate mild to extreme pain since ancient times. The extraction of pharmaceutically important alkaloids like morphine and codeine from poppy plant reflects the need for the most suitable and standard methods. Several analytical and extraction techniques have been reported in open literature for morphine, codeine and other important alkaloids which play a vital function in drug development and drug discovery. Many studies suggest that opioids are also responsible for adverse effects or secondary complications like dependence and withdrawal. In recent years, opium consumption and addiction are the most important risk factors. Many evidence-based reviews suggest that opium consumption is directly linked or acts as a risk factor for different cancers. In this review, we highlight significant efforts related to research which have been done over the past 5 decades and the complete information on Papaver somniferum including its phytochemistry, pharmacological actions, biosynthetic pathways and analytical techniques of opium alkaloid extraction and the link between opium consumption and cancer-related updates.

Magnetic material based on mesostructured silica functionalized with β-cyclodextrin to extract opium alkaloids in poppy seed infusions

Magnetic material based on mesostructured silica functionalized with β-cyclodextrin to extract opium alkaloids in poppy seed infusions

Insight into the Impact of Food Processing and Culinary Preparations on the Stability and Content of Plant Alkaloids Considered as Natural Food Contaminants

Pyrrolizidine alkaloids, tropane alkaloids and opium alkaloids are natural plant toxins that have recently gained special interest in food safety due to their concerning occurrence in many foods and feeds. Although a legislation for these alkaloids has recently been established, the concentration levels of these toxins in food exceed in many cases the maximum limit established by the competent authorities. Moreover, these regulations only establish maximum limits of these compounds for certain raw materials, but processed products are generally not considered. However, it is important to correctly assess the potential health risk of these alkaloids through the diet. Accordingly, this review aims to provide insight into these alkaloids and give an overview on how food processing and culinary preparation can influence their content and stability. For this purpose, the most relevant works that address the effect of heat treatment, fermentation, infusion preparation (transfer rate) and other treatments (milling, washing and soaking) on these natural toxins are reviewed. To date, this research field has been scarcely studied and many of the results published are contradictory, so it is not always possible to establish conclusive findings. In many cases, this is due to a lack of experimental design and exhaustive control of the different variables that may affect these treatments and preparations. Likewise, considering the transformation of these alkaloids into toxic degradation products it is also of high interest. Therefore, further studies are needed to delve deeper into the stability of these toxins and to understand how their content may be affected by the transformation of contaminated raw materials into processed products, so that the risk exposure of the population to these alkaloids through diet can be determined more precisely. Hence, this topic constitutes a research line of great interest for future works with many challenges to be resolved.

Evaluation of the Transfer and Occurrence of Opium Alkaloids in Poppy Seed Teas Using Preconcentrations with µSPEed® Followed by GC-MS Analysis

Intoxication due to the consumption of poppy seed teas has been reported due to their contamination with opium alkaloids (OAs). In this work, an efficient methodology based on microsolid-phase extraction (µSPEed®) followed by gas chromatography–mass spectrometry (GC-MS) has been optimized to quantify five OAs in poppy seed teas. Nine cartridges (C4, C8, C18, silica, APS, PFAs, PS/DVB-RP, PS/DVB-SCX and PS/DVB-SAX), pH levels, cycles and elution solvents were evaluated. The method was validated and applied to study the transfer of OAs by evaluating water temperatures, infusion times and seed amounts. The highest transfer rates (71% for morphine, 96% for thebaine, and 100% for codeine, noscapine and papaverine) were achieved at 90°C, 5 min, with 4 g. These conditions were used to quantify the OAs in four teas prepared from different seeds. A high amount of morphine (1563 µg/L) was found in one tea, indicating that the seeds had a concentration twice the maximum limit, highlighting the need to warn the population of this dangerous practice.