Methylenedioxy Derivatives Research Articles

Structure Activity Relationship Studies of Psychostimulant Synthetic Cathinones Reveal Nanomolar Antagonist Potency of α‐Pyrrolidinohexiophenone (α‐PHP) at Human Muscarinic M2Receptors

Synthetic cathinones (SCs), psychostimulant drugs of abuse, are β‐keto analogs of amphetamine that primarily target monoamine transporters as inhibitors or substrates. Certain pyrrolidine‐containing SCs, such as α‐Pyrrolidinohexiophenone (α‐PHP) and methylenedioxypyrovalerone (MDPV), are potent monoamine transporter inhibitors that appear to produce distinct toxic, autonomic—e.g., tachycardia and arrythmia—and neuropsychiatric—e.g., delirium and cognitive impairments—adverse events compared to N‐alkylated SCs and amphetamines, which are monoamine transporter substrates. Although the apparent differences in toxicity could be caused by unique pharmacodynamic effects at monoamine transporters, we hypothesized there is another mechanism. We focused on muscarinic receptors (MRs), as numerous MR antagonists are well‐characterized deliriants that also cause tachycardia. We conducted pharmacological assays assessing human M1, M2, M3, M4, and M5R activity of 10 pyrrolidine‐containing SCs, systematically evaluating the effect of the α‐carbon chain length of methylenedioxy‐containing and unsubstituted α‐propiophenone analogues. [3H]Scopolamine competition binding assays revealed that increasing the α‐carbon chain length of unsubstituted, but not methylenedioxy derivatives led to a stepwise enhancement in affinity (Ki) at all MR subtypes, with highest affinities typically observed at M2Rs. Relative to all other SCs tested, α‐PHP had the highest affinity at M2Rs, with a calculated pKi of 6.28 (Ki= 520 nM). We next assessed the M2R functional effects of α‐PHP using M2R—cAMP and M2R—β‐arrestin recruitment assays; α‐PHP behaved as an M2R competitive antagonist in both assays. α‐PHP antagonized oxotremorine‐elicited cAMP inhibition with an apparent pKb of 7.29 (Kb= 50 nM) and antagonized oxotremorine‐elicited β‐arrestin recruitment with an apparent pKb of 6.22 (Kb= 602 nM). Toxicology studies report that serum concentrations of commonly abused pyrrolidine‐containing SCs, including α‐PHP, can range from 713 to 2,619 nM. Thus, α‐PHP’s potency at M2Rs is physiologically relevant and likely contributes to its toxicity. Given the dominant function of M2Rs to slow heart rate, α‐PHP may cause tachycardia, in part, by inhibition of cardiac M2Rs. This inhibitory effect on the parasympathetic nervous system, in combination with sympathomimetic effects caused by monoamine transporter inhibition could explain the serious adverse cardiovascular events associated with certain pyrrolidine‐containing SCs.Support or Funding InformationFunding: NIDA R21DA040907

Synthesis and anticancer activities of polymethylenedioxy analogues of combretastatin A-2

Combretastatin A-4 is a highly potent natural stilbene that can inhibit cancer cell proliferation. Numerous analogues of combretastatin A-4 have been proposed for clinical applications. However, structural studies of combretastatin A-2, a methylenedioxy derivative of combretastain A-4, are not available. In this study, various analogues of combretastatin A-2 with polymethylenedioxy spacer were prepared and their antiproliferative activities to four human cancer cell lines (HeLa, SK-OV-3, A549, and HT-29) and two normal cells (HaCaT and MDCK) were evaluated. Binding characteristics were evaluated based on computational docking and previously reported experimental data. Results suggest that their binding conformations are highly dependent on steric volume and electrostatic properties of substituents.

Design, synthesis and identification of novel coumaperine derivatives for inhibition of human 5-LOX: Antioxidant, pseudoperoxidase and docking studies.

5-Lipoxygenase (5-LOX) is a key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes, leading to asthma. Developing potent 5-LOX inhibitors especially, natural product based ones, are highly attractive. Coumaperine, a natural product found in white pepper and its derivatives were herein developed as 5-LOX inhibitors. We have synthesized twenty four derivatives, characterized and evaluated their 5-LOX inhibition potential. Coumaperine derivatives substituted with multiple hydroxy and multiple methoxy groups exhibited best 5-LOX inhibition. CP-209, a catechol type dihydroxyl derivative and CP-262-F2, a vicinal trihydroxyl derivative exhibited, 82.7% and 82.5% inhibition of 5-LOX respectively at 20 µM. Their IC50 values are 2.1 ± 0.2 µM and 2.3 ± 0.2 µM respectively, and are comparable to zileuton, IC50 = 1.4 ± 0.2 µM. CP-155, a methylenedioxy derivative (a natural product) and CP-194, a 2,4,6-trimethoxy derivative showed 76.0% and 77.1% inhibition of 5-LOX respectively at 20 µM. Antioxidant study revealed that CP-209 and 262-F2 (at 20 µM) scavenged DPPH radical by 76.8% and 71.3% respectively. On the other hand, CP-155 and 194 showed very poor DPPH radical scavenging activity. Pseudo peroxidase assay confirmed that the mode of action of CP-209 and 262-F2 were by redox process, similar to zileuton, affecting the oxidation state of the metal ion in the enzyme. On the contrary, CP-155 and 194 probably act through some other mechanism which does not involve the disruption of the oxidation state of the metal in the enzyme. Molecular docking of CP-155 and 194 to the active site of 5-LOX and binding energy calculation suggested that they are non-competitive inhibitors. The In-Silico ADME/TOX analysis shows the active compounds (CP-155, 194, 209 and 262-F2) are with good drug likeliness and reduced toxicity compared to existing drug. These studies indicate that there is a great potential for coumaperine derivatives to be developed as anti-inflammatory drug.

Pooled human liver preparations, HepaRG, or HepG2 cell lines for metabolism studies of new psychoactive substances? A study using MDMA, MDBD, butylone, MDPPP, MDPV, MDPB, 5-MAPB, and 5-API as examples

Metabolism studies play an important role in clinical and forensic toxicology. Because of potential species differences in metabolism, human samples are best suitable for elucidating metabolism. However, in the case of new psychoactive substances (NPS), human samples of controlled studies are not available. Primary human hepatocytes have been described as gold standard for in vitro metabolism studies, but there are some disadvantages such as high costs, limited availability, and variability of metabolic enzymes. Therefore, the aim of our study was to investigate and compare the metabolism of six methylenedioxy derivatives (MDMA, MDBD, butylone, MDPPP, MDPV, MDPB) and two bioisosteric analogues (5-MAPB, 5-API) using pooled human liver microsomes (pHLM) combined with cytosol (pHLC) or pooled human liver S9 fraction (pS9) all after addition of co-substrates for six phase I and II reactions. In addition, HepaRG and HepG2 cell lines were used. Results of the different in vitro tools were compared to each other, to corresponding published data, and to metabolites identified in human urine after consumption of MDMA, MDPV, or 5-MAPB. Incubations with pHLM plus pHLC showed similar results as pS9. A more cost efficient model for prediction of targets for toxicological screening procedures in human urine should be identified. As expected, the incubations with HepaRG provided better results than those with HepG2 concerning number and signal abundance of the metabolites. Due to easy handling without special equipment, incubations with pooled liver preparations should be the most suitable alternative to find targets for toxicological screening procedures for methylenedioxy derivatives and bioisosteric analogues.

Tuning the Solution Phase Photophysics of Two De Novo Designed Hydrogen Bond Sensitive 9-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one Derivatives

Two new fluorophores, 6,7-dimethoxy-9-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one (DMTCO) and 5-methyl-8,9-dihydro-5H-[1,3]dioxolo[4,5-b]carbazol-6(7H)-one (MDDCO), first of their kind, have been synthesized from the corresponding methoxy and methylenedioxy derivatives of 2,3,4,9-tetrahydro-1H-carbazol-1-one respectively. Comprehensive photophysical characterization of these compounds has been carried out in sixteen different homogeneous solvents and binary solvent mixtures. Both of these compounds are sensitive to solvent polarity, but the sensitivity is much higher in electronic excited state observed by steady-state and time-resolved fluorescence experiments than in ground state studied by UV-vis absorption spectroscopy. The fluorescence spectral shifts are linearly correlated with the empirical parameters of the protic solvents and also the quantitative influence of the empirical solvent parameters on the emission maxima of the compounds has been calculated. The change in dipole moment of the compounds in their excited state has been calculated from the shifts in corresponding emission maxima in pure solvents. A higher dipole moment change of both DMTCO and MDDCO in protic solvents is due to intermolecular hydrogen bonding which is further confirmed by the comparison of their behaviour in toluene-acetonitrile and toluene-methanol solvent mixtures. From structural features, MDDCO is more planar compared to DMTCO, which is reflected better in fluorescence quenching of the former with organic bases, N,N-dimethylaniline and N,N-diethylaniline. Laser flash photolysis experiments prove that the quenching interaction originates from photoinduced electron transfer from the bases to the compounds.

Synthesis and Evaluation of Novel Fluorinated 2‐Styrylchromones as Antibacterial Agents

A range of fluorinated 2‐styrylchromones (5a–g) of which six were new (5a–f) were prepared in three steps using the Baker‐Venkataraman rearrangement along with two methoxylated derivatives (5h-i) and a methylenedioxy derivative (5j) and screened for their antibacterial activity using Gram‐positive bacteria (Staphylococcus aureus, sciuri, and xylosus as well as Bacillus subtilis) and Gram‐negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia). The compounds were most effective against B. subtilis followed by S. aureus and a single strain of E. coli (ATCC 25922). Difluorination on the phenyl ring was shown to enhance antibacterial activity, and fluorine substitution at the 6 position was shown to be far superior to substitution at the 7 position. In comparison to tetracycline, the activity indices of the fluorinated styrylchromones ranged from 0.50 to 0.75 against B. subtilis. The crystal structure of 2′‐fluoro‐2‐styrylchromone is also presented, and the molecule was shown to be planar.

Exploring Nitrostyrene as a Scaffold for a New Class a of Monoamine Oxidase Inhibitors

With the ultimate purpose of finding out the structural features that are relevant for MAO inhibitory activity and selectivity towards MAO-B isoform, a series of compounds encompassing a β-nitrostyrene moiety was designed and the in vitro inhibitory activity was evaluated. In the present work, we report the synthesis and the pharmacological evaluation of a series of functionalized derivatives of β-methyl-β-nitrostyrene with distinct substitution patterns in the phenyl ring, namely hydroxyl, methoxy, benzyloxy and methylenedioxy. All the studied compounds were substituted in meta and para positions of the phenyl ring related to the nitrovinyl side chain. The synthesized compounds were evaluated towards both human MAO isoforms, displaying some of them activities in the low micromolar range. Particularly compound 6 (a methylenedioxy derivative) exhibits high potency and selectivity towards MAO-B.

Optimization and validation of CEDIA drugs of abuse immunoassay tests in serum on Hitachi 912

Due to sensitive limits of detection of chromatographic methods and low limit values regarding the screening of drugs under the terms of impairment in safe driving (§ 24a StVG, Street Traffic Law in Germany), preliminary immunoassay (IA) tests should be able to detect also low concentrations of legal and illegal drugs in serum in forensic cases. False-negatives should be avoided, the rate of false-positive samples should be low due to cost and time. An optimization of IA cutoff values and a validation of the assay is required for each laboratory. In a retrospective study results for serum samples containing amphetamine, methylenedioxy derivatives, cannabinoids, benzodiazepines, cocaine (metabolites), methadone and opiates obtained with CEDIA drugs of abuse reagents on a Hitachi 912 autoanalyzer were compared with quantitative results of chromatographic methods (gas or liquid chromatography coupled with mass spectrometry (GC/MS or LC/MS)). Firstly sensitivity, specificity, positive and negative predictive values and overall misclassification rates were evaluated by contingency tables and compared to ROC-analyses and Youden-Indices. Secondly ideal cutoffs were statistically calculated on the basis of sensitivity and specificity as decisive statistical criteria with focus on a high sensitivity (low rates of false-negatives), i.e. using the Youden-Index. Immunoassay (IA) and confirmatory results were available for 3014 blood samples. Sensitivity was 90% or more for nearly all analytes: amphetamines (IA cutoff 9.5 ng/ml), methylenedioxy derivatives (IA cutoff 5.5 ng/ml), cannabinoids (IA cutoff 14.5 ng/ml), benzodiazepines (IA cutoff >0 ng/ml). Test of opiates showed a sensitivity of 86% for a IA cutoff value of >0 ng/ml. Values for specificity ranged between 33% (methadone, IA cutoff 10 ng/ml) and 90% (cocaine, IA cutoff 20 ng/ml). Lower cutoff values as recommended by ROC analyses were chosen for most tests to decrease the rate of false-negatives. Analyses enabled the definition of cutoff values with good values for sensitivity. Small rates of false-positives can be accepted in forensic cases.

Molecular Modelling and Antipoliovirus Activity of Some Isoquinoline Alkaloids

In an attempt to understand the antipoliovirus activity of some isoquinoline alkaloids, a molecular modelling survey was performed. The antipoliovirus activity of various aporphines is related to the structural features induced by the C1 and C2 isoquinoline substituents. In this work, the unexpected activity of two methylenedioxy derivatives, as well as the distinct activity of two benzylisoquinolines, secoderivatives of aporphines, are explained using field fit techniques. The results suggest that the 10-methoxy substituent linked to the tetrahydronaphthalene moiety of aporphines is also of importance for their antipoliovirus activity.

Sweat as an Alternative Matrix for Amphetamines and MethylenEdioxy Derivatives Analysis

Analysis of drugs and metabolites in biological alternative matrices such as sweat is getting importance in forensic toxicology for workplace drug testing, criminal justice, drug abuse treatment and sport doping control programs. The consumption of 3,4-Methylenedioxymethamphetamine (MDMA), or “ecstasy”, a commonly abused synthetic psychoactive substance as well as other sympathomimetic amines including amphetamine and methamphetamine is widespread and increasingly popular among young people in the United States and Europe, becoming a very serious public health problem. This paper reviews the use of sweat samples for amphetamines and methylenedioxy derivatives analysis, methodologies and studies involved subjects and controlled administration of MDMA. According to guidelines for drug monitoring using sweat as alternative specimens proposed by the Substance Abuse and Mental Health Services Administration (SAMHSA) in 2004, requirements for a positive sweat test include amphetamines screen test with ≥ 25 ng/patch, and a confirmation cutoff of 25 ng/patch for amphetamines and methylenedioxy derivatives. A review of the indexed literature found respectively limits of detection and quantification ranging from 0.72 ng/patch to 5 ng/patch and from 1.4 ng/patch to 5 ng/patch for all analytes.

Stability Studies of Principal Illicit Drugs in Oral Fluid: Preparation of Reference Materials for External Quality Assessment Schemes

Data on the stability of drugs of abuse in oral fluid are needed to define the optimal transportation and storage conditions when this biological fluid has to be used for off-site screening and confirmation analyses, as well as in the preparation of reference material for external quality assessment schemes. The short-term and long-term stability of opiates, cocaine, amphetamines, and methylenedioxy derivatives in unstimulated oral fluid was evaluated in different storage conditions, with and without the addition of citrate buffer and sodium azide. Short-term stability was evaluated at 25 degrees C and 37 degrees C for up to 7 days. Long-term stability was evaluated at different time intervals for up to 2 months at 4 degrees C and -20 degrees C. The effect of three different freezing and thawing cycles was also studied. No significant loss of amphetamines and methylenedioxy derivatives, morphine, codeine, and benzoylecgonine was observed under any of the investigated conditions. Conversely, hydrolysis of the ester bonds of cocaine and 6-MAM, leading to the formation of benzoylecgonine and morphine, respectively, was observed under all the applied conditions when oral fluid was not buffered and preserved. The addition of citrate buffer (pH, 4) and sodium azide (0.1%) to oral fluid prevented their degradation during up to 7 days of storage at 25 degrees C and 37 degrees C and up to 2 months at 4 degrees C and -20 degrees C. The stability of the principal illicit drugs spiked in buffered and stabilized oral fluid is adequate for transportation of collected samples at ambient temperature and for shipment and storage of reference materials for external quality assessment schemes.

Apparent active transport of MDMA is not mediated by P‐glycoprotein: a comparison with MDCK and Caco‐2 monolayers

Amphetamines and their methylenedioxy derivatives generically display similar behavioral, physiologic and toxic effects. Inconsistent pharmacokinetic and toxicity data for methylenedioxymethamphetamine (MDMA) may suggest that active drug transporters are interacting with these compounds, and thus altering drug absorption and tissue distribution. In vitro models of CNS accumulation and intestinal drug transport were used to assess efflux transport of MDMA. Madin-Darby kidney cell epithelial (MDCK) monolayers displayed a 4-fold increase in accumulation in the basolateral to apical orientation relative to the apical to basolateral orientation, although no differential accumulation was noted between MDCK-WT and MDCK-MDR1 monolayers. Caco-2 monolayers demonstrated an approximate 2-fold increase in accumulation of MDMA. Exposure of various inhibitors of active drug transporters demonstrated mixed results; ritonavir, progesterone and indomethacin produced an approximately 50% reduction of MDMA transport, while verapamil, MK-571 and probenecid had no effect. Based on these data, it is concluded that MDMA efflux is mediated via the activity of a transporter distinct from P-glycoprotein. The possible inhibitory effects of amphetamines on rhodamine-123 transport were also assessed. MDMA, methylenedioxyamphetamine, amphetamine and methamphetamine, at physiologically relevant concentrations, did not significantly alter the transport of rhodamine-123 in Caco-2 monolayers or the LS180 cell line, suggesting that these compounds do not alter the function of P-glycoprotein.

Poly(methacrylic acid-ethylene glycol dimethacrylate) monolith in-tube solid phase microextraction coupled to high performance liquid chromatography and analysis of amphetamines in urine samples

In-tube solid-phase microextraction (SPME) based on a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column was investigated for the extraction of amphetamine, methamphetamine and their methylenedioxy derivatives. The monolithic capillary column showed high extraction efficiency towards target analytes, which could be attributed to its larger loading amount of extraction phase than conventional open-tubular extraction capillaries and the convective mass transfer procedure provided by its monolithic structure. The extraction mechanism was studied, and the results indicated that the extraction process of the target analytes was involved with hydrophobic interaction and ion-exchange interaction. The polymer monolith in-tube SPME-HPLC system with UV detection was successfully applied to the determination of amphetamine, methamphetamine and their methylenedioxy derivatives in urine samples, yielding the detection limits of 1.4–4.0 ng/mL. Excellent method reproducibility (RSD < 2.9%) was found over a linear range of 0.05–5 μg/mL, and the time for the whole analysis was only ∼25 min. The monolithic capillary column was reusable in coping with the complicated urine samples.

Development and validation of a high-performance liquid chromatography-mass spectrometry assay for determination of amphetamine, methamphetamine, and methylenedioxy derivatives in meconium.

A procedure based on liquid chromatography-mass spectrometry (LC-MS) is described for determination of amphetamine, methamphetamine, and methylendioxy derivatives in meconium, using 3,4-methylendioxypropylamphetamine as internal standard. The analytes were initially extracted from the matrix by 17 mM methanolic HCl. Subsequently, a solid-phase extraction with Bondelut Certify columns was applied. Chromatography was performed on a C(18) reversed-phase column using a linear gradient of 10 mM ammonium bicarbonate, pH 9.0-methanol as a mobile phase. Analytes were determined in LC-MS single ion monitoring mode with an atmospheric pressure ionization-electrospray interface. The method was validated in the range 0.005-1.00 microg/g using 1 g of meconium per assay. Mean recoveries ranged between 61.1 and 87.2% for different analytes. The quantification limits were 0.005 microg/g meconium for amphetamine, methamphetamine, and 4-hydroxy-3-methoxymethamphetamine and 0.004 microg/g meconium for 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyethylamphetamine, and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine. The method was applied to analysis of meconium in newborns to assess eventual fetal exposure to amphetamine derivatives.

Development and validation of a gas chromatography-mass spectrometry assay for hair analysis of amphetamine, methamphetamine and methylenedioxy derivatives

A procedure based on gas chromatography-mass spectrometry (GC-MS) is described for the determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-methylenedioxyethylamphetamine (MDE or MDEA) and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in hair. Hair samples were digested with 1 M sodium sulfide at 37 °C (by shaking for 3 h and was kept at room temperature overnight), and extracted with two sequential extraction procedures: liquid-liquid extraction with tert-butyl methyl ether and solid-phase extraction with Bond-Elut Certify columns. Extracted analytes were derivatised with N-methyl-bis(trifluoroacetamide), separated by a 5% phenylmethylsilicone column and determined by a mass spectrometer detector in selected ion monitoring mode. A good reproducibility (intra-assay R.S.D.=1.5–15.7%), accuracy (intra-assay error=2.0–11.7%) and sensitivity (LOD=0.03–0.08 ng/mg hair) were attained. The method was successfully applied to the analysis of the proximal (1 cm) hair segment to assess recent self-reported use in “ecstasy” consumers. Otherwise, further studies are needed to validate methodology developed in case of amphetamine consumption.

Quantitation of Amphetamine, Methamphetamine, and Their Methylenedioxy Derivatives in Urine by Solid-Phase Microextraction Coupled with Electrospray Ionization−High-Field Asymmetric Waveform Ion Mobility Spectrometry−Mass Spectrometry

Amphetamine, methamphetamine, and their methylenedioxy derivatives have been identified and measured in a human urine matrix using solid-phase microextraction (SPME) and high-field asymmetric waveform ion mobility spectrometry (FAIMS) in combination with electrospray ionization (ESI) and mass spectrometric detection (MS). Limits of detection in human urine between 200 pg/mL and 7.5 ng/mL have been achieved. The use of a simple extraction method, SPME, combined with the high sensitivity and selectivity of ESI-FAIMS-MS eliminates the need for chromatographic separation and allows for very rapid sample processing.

Determination of stimulants in human urine and hair samples by polypyrrole coated capillary in-tube solid phase microextraction coupled with liquid chromatography-electrospray mass spectrometry

A simple and sensitive method for the determination of amphetamine, methamphetamine and their methylenedioxy derivatives in urine and hair samples was developed by coupling automated in-tube solid phase microextraction (SPME) to high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ES-MS). To achieve optimum performance, the conditions for both the in-tube SPME and the ES-MS detection were investigated. ES-MS detection conditions were studied by flow injection analysis (FIA) with direct liquid injection. In-tube SPME conditions were optimized by selecting the appropriate extraction parameters, including capillary stationary phases and sample pH. For the compounds studied, a custom-made polypyrrole (PPY) coated capillary showed superior extraction efficiency as compared to commercial capillaries. Therefore, the PPY coated capillary was selected for in-tube SPME in this study. The calibration curves of stimulants were linear in the range from 0.1 to 100 ng ml −1 with detection limits (S/N=3) of 8–56 ng l −1. This method was successfully applied to the analysis of the stimulants in spiked human urine and hair samples.

Enantiospecific synthesis of 8-epipuupehedione from (R)-(−)-carvone

An enantiospecific synthesis of the antitumor marine sponge metabolite puupehedione (2a) and its C8-epimer 2b as their methylenedioxy derivatives 8a and 8b was achieved through concomitant O-allyl deprotection and electrocyclization of 20 derived from (−)-carvone.

Simple and rapid determination of amphetamine, methamphetamine, and their methylenedioxy derivatives in urine by automated in-tube solid-phase microextraction coupled with liquid chromatography-electrospray ionization mass spectrometry.

A simple and rapid method for the determination of amphetamine, methamphetamine, and their 3,4-methylenedioxy derivatives in urine samples was developed using automated in-tube solid-phase microextraction (SPME) coupled with liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). In-tube SPME is an extraction technique for organic compounds in aqueous samples in which analytes are extracted from the sample directly into an open tubular capillary by repeated draw/eject cycles of sample solution. LC-MS analyses of stimulants were initially performed by liquid injection onto an LC column to determine spectra. Five stimulants tested in this study gave very simple ESI mass spectra, and strong signals corresponding to [M+H]+ were observed for all stimulants. The stimulants were well separated with a Supelcosil LC-CN column using acetonitrile/50mM ammonium acetate (15:85) as a mobile phase. In order to optimize the extraction of stimulants, several in-tube SPME parameters were examined. The optimum extraction conditions were 15 draw/eject cycles of 35 microL of sample in 50mM Tris-HCI (pH 8.5) at a flow rate of 100 microL/min using an Omegawax 250 capillary column. The stimulants extracted by the capillary were easily desorbed by mobile phase flow, and carryover of stimulants was not observed. Using in-tube SPME-LC-ESI-MS with selected ion monitoring, the calibration curves of stimulants were linear in the range from 2 to 100 ng/mL with correlation coefficients above 0.9985 (n = 18) and detection limits (S/N = 3) of 0.38-0.82 ng/mL. This method was successfully applied to the analysis of human urine samples without interference peaks. The recoveries of stimulants spiked into urine samples were above 81%.

ChemInform Abstract: Synthesis and Cytotoxic Activity of Pyranophenanthridine Analogues of Fagaronine and Acronycine.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.