MDA) And 3,4-methylenedioxymethamphetamine Research Articles

Novel electrochemical-surface plasmon resonance (EC-SPR) sensor for amphetamine-type stimulants detection based on molecularly imprinted strategy

The abuse of amphetamine-type stimulants (ATS) has always been a worldwide problem and the law enforcement agencies are tasked and demanded with identifying them on-site rapidly and reliably in unknown samples. In the present study, an efficient electrochemical-surface plasmon resonance (EC-SPR) sensor, coupled with molecularly imprinted strategy, for adsorption and quantitative measurement of ATS in the human urine and serum samples was demonstrated. The molecular imprinted recognition system on SPR chip was synthesized by a convenient one-step electrochemical polymerization with 3,4-methylenedioxyphenethylamine (MDEA) as the template molecule and dopamine (DA) as the functional monomer. In particular, the molecularly imprinted process was regulated and controlled through synchronous measurement of the SPR signals. This proposed method showed lower detection limit with 57 nM and 59 nM for 3,4-methylenedioxeamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in broad linearity, respectively and could be resistant to the interferences from various illicit drugs and other substances. Moreover, this EC-SPR sensor could be employed for detection the spiked MDMA in real urine and serum samples, significantly exhibiting attractive application prospect in forensic analysis.

Gas chromatography-mass spectrometry (GC-MS) analysis of amphetamine, methamphetamine, 3,4-methylenedioxy-amphetamine and 3,4-methylenedioxymethamphetamine in human hair and hair sections

In this paper, the authors describe a sensitive method for simultaneous quantitation of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in human hair by gas chromatography-mass spectrometry (GC-MS). Hair samples are initially cut into 0.5-cm sections, washed with methanol, and digested for 1 hr at 80°C in 2 N NaOH and deuterated internal standards. The resulting solutions are processed with a liquid-liquid extraction procedure and further derivatized with heptafluorobutyric anhydride (HFBA) before undergoing GC/MS analysis. The overall protocol achieves the following results when applied to the analysis of 50 mg drug-free hair specimens fortified with 2-40 ng/mg amphetamines: recovery: 77.45-86.86%; inter-day and intra-day precision ranges: 0.55-7.73% and 0.76-4.79%, respectively; linearity: r2 > 0.997; detection limits: 0.05 ng/mg for AM, MA, and MDMA and 0.1 ng/mg for MDA; and quantitation limits: 0.1 ng/mg for AM, MA, and MDMA and 0.2 ng/mg for MDA. Data derived from our analysis of hair samples collected from 30 self-reported methamphetamine abusers range from 1.39 to 15.41 (mean ± S.D., 5.21 ± 3.25) ng/mg for amphetamine and 12.58 to 173.28 (mean ± S.D., 56.10 ± 36.85) ng/mg for methamphetamine. This method has also been utilized successfully to evaluate the deposition pattern of drugs in head hairs collected from six female methamphetamine abusers staying at a rehabilitation facility. We conclude that this relatively simple protocol can be used for routine and reliable identification and quantitation of AM, MA, MDA, and MDMA in hair.

Rapid Analysis of Four Amphetamines in Urine by Self-Made Pipette-Tip Solid-Phase Extraction Followed by GC-MS/MS.

A simple and rapid pipette-tip solid-phase extraction (PT-SPE) procedure with derivatization prior to gas chromatography triple quadrupole mass spectrometry analysis is developed for the simultaneous determination of amphetamine (AMP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in urine samples. The PT-SPE procedure using self-made sorbent could extract drugs within 6min from 100-μL urine samples, requiring low solvent-consumption (<2.0mL). Besides, the self-made pipette tip could be reused at least five times. Under optimized conditions, the recoveries of four amphetamines at spiked levels (low, medium and high) ranged from 87.7 to 110.4%, with relative standard deviations<9.5%. The limit of detections and limit of quantifications for AMP, MA, MDA and MDMA were in the range of 2.52-8.25ng⋅mL-1 and 8.4-27.5ng⋅mL-1, respectively. Validation results show that the proposed method is suitable for the quantitation of amphetamines and has been successfully applied in the urine samples of suspected drug abusers.

Single analyzer precursor scans using an ion trap.

Precursor ion and neutral loss scans are general survey methods of tandem mass spectrometry (MS/MS) used for detecting structurally related compounds. Until now they have been performed in multiple analyzer instruments, e.g. triple quadrupoles and hybrid MS/MS instruments. Implementation of precursor ion scans in single mass analyzers would be advantageous in reducing instrument complexity. Adoption of secular frequency scanning as a method of mass-selective excitation is shown to enable precursor scans in a single ion trap in a miniature mass spectrometer. A small supplementary alternating current (ac) signal is swept in frequency so as to cause mass-selective excitation of trapped ions. Simultaneously, a higher fixed amplitude ac signal is applied at the fixed secular frequency of a product ion, ejecting the mass-selected product ion and providing temporal data corresponding to a precursor ion spectrum. Precursor scanning in a single ion trap is demonstrated using a mixture of three illicit drugs: cocaine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA). Acquisition of the spectra as a function of the frequency of the product ejection waveform demonstrates that the signals acquired represent precursor ion scans. Secular frequency scanning is a nonconventional method of mass scanning that in combination with product ion ejection enables precursor scans in single ion traps. This phenomenon is demonstrated here for a miniature linear ion trap, but the concepts described also apply to quadrupole mass filters. Copyright © 2016 John Wiley & Sons, Ltd.

MALDI–TOF mass spectrometric determination of four amphetamines in blood

A rapid and sensitive detection method using matrix-assisted laser desorption ionization time-of-flight mass spectrometry was developed for the analysis of amphetamine (A), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA). In this method, α-cyano-4-hydroxy cinnamic acid was used as the matrix to assist the ionization of amphetamines. The MS spectra of these amphetamines showed protonated molecules [M + H]+ and fragment ions with comparable or higher intensities. The quantifications of A and MA were performed using A-d 7 and MA-d 5 as the internal standard, respectively, and those of MDA and MDMA were performed using MDMA-d 5 as the internal standard. The limit of detection and the quantification range using 20 μl of blood were about 10 ng/ml and 30–500 ng/ml for A and MDA, respectively, and about 1 ng/ml and 3–50 ng/ml for MA and MDMA, respectively. In two cases of poisoning in which MA was abused, the levels of A in blood and urine were from 0.050 to 3.24 μg/ml and the levels of MA were from 0.231 to 25.1 μg/ml.

MAE–GC Determination of Methamphetamine, 3,4-Methylenedioxyamphetamine and 3,4-Methylenedioxymethamphetamine in Human Urine

Methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) were extracted from human urine by using microwave-assisted extraction (MAE) followed by gas chromatography analysis with flame ionization detection. In order to improve the extraction efficiency, experimental parameters on the extraction, including extraction solvent and its volume, pH value of sample, extraction time and temperature were investigated. Under the optimal conditions, the average recoveries of MA, MDA and MDMA were 92.25, 85.94 and 91.50%, respectively. And the intra-day and inter-day relative standard deviations were not greater than 6.9%. The results indicate that the developed method is rapid, accurate and sensitive, and can be used for the simultaneous determination of MA, MDA and MDMA in urine for forensic application.

Simultaneous determination of amphetamine-type stimulants and cannabinoids in fingernails by gas chromatography-mass spectrometry

A gas chromatography-mass spectrometric (GC-MS) method was developed and validated for the simultaneous detection and quantification of four amphetamine-type stimulants (amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA)) and two cannabinoids (Delta9-tetrahydrocannabinol (Delta9-THC) and 11-nor-Delta9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH)) in fingernails. Fingernail clippings (30 mg) were washed with distilled water and methanol, and then incubated in 1.0 M sodium hydroxide at 95 degrees C for 30 min. The compounds of interest were isolated by liquid-liquid extraction followed by derivatization with N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) at 70 degrees C for 15 min. The derivatized compounds were analyzed by GC-MS in the selective ion monitoring (SIM) mode. The linear ranges were 0.1-15.0 ng/mg for AP, 0.2-15.0 ng/mg for MDA, Delta9-THC and THCCOOH, and 0.2-30.0 ng/mg for MA and MDMA, with good correlation coefficients (r2 > 0.9991). The intra-day, inter-day, and inter-person precisions were within 10.6%, 6.3%, and 5.3%, respectively. The intra-day, inter-day and inter-person accuracies were between -6.1 and 5.0%, -6.2 and 5.7%, and -6.4 and 5.6%, respectively. The limits of detection (LODs) and quantification (LOQs) for each compound were lower than 0.056 and 0.2 ng/mg, respectively. The recoveries were in the range of 74.0-94.8%. Positive GC-MS results were obtained from specimens of nine suspected MA or cannabis abusers. The concentration ranges of MA, AP, and THCCOOH were 0.10-1.41, 0.12-2.64, and 0.20 ng/mg, respectively. Based on these results, the method proved to be effective for the simultaneous qualification and quantification of amphetamine-type stimulants and cannabinoids in fingernails.

Stability studies of amphetamine and ephedrine derivatives in urine

Knowledge of the stability of drugs in biological specimens is a critical consideration for the interpretation of analytical results. Identification of proper storage conditions has been a matter of concern for most toxicology laboratories (both clinical and forensic), and the stability of drugs of abuse has been extensively studied. This concern should be extended to other areas of analytical chemistry like antidoping control. In this work, the stability of ephedrine derivatives (ephedrine, norephedrine, methylephedrine, pseudoephedrine, and norpseudoephedrine), and amphetamine derivatives (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA)) in urine has been studied. Spiked urine samples were prepared for stability testing. Urine samples were quantified by GC/NPD or GC/MS. The homogeneity of each batch of sample was verified before starting the stability study. The stability of analytes was evaluated in sterilized and non-sterilized urine samples at different storage conditions. For long-term stability testing, analyte concentration in urine stored at 4 degrees C and -20 degrees C was determined at different time intervals for 24 months for sterile urine samples, and for 6 months for non-sterile samples. For short-term stability testing, analyte concentration was evaluated in liquid urine stored at 37 degrees C for 7 days. The effect of repeated freezing (at -20 degrees C) and thawing (at room temperature) was also studied in sterile urine for up to three cycles. No significant loss of the analytes under study was observed at any of the investigated conditions. These results show the feasibility of preparing reference materials containing ephedrine and amphetamine derivatives to be used for quality control purposes.

Confirmation of amphetamine, methamphetamine, MDA and MDMA in urine samples using disk solid-phase extraction and gas chromatography–mass spectrometry after immunoassay screening

A method using mixed phase disk solid-phase extraction (SPE) and gas chromatography–mass spectrometry (GC–MS) was developed for confirmation of amphetamine (AMP), methamphetamine (MET), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in urine samples after immunoassay screening. Disk SPE provided hydrophobic (C 18) and strong cation-exchange (SCX) interactions. The analytes were retained on SCX functional groups in the disk and eluted with ammoniated ethyl acetate after washed with methanol. Confirmation and quantitation was exercised by selected ion monitoring using nikethamide as chromatographic standard. Recoveries of the amphetamines were between 73.0 and 104.6% with RSDs in range of 2.1–6.4% ( n=3). The limits of detection were 2 ng/ml for AMP, MET and MDMA, and 4 ng/ml for MDA. Five real urine samples were tested with the method after immunoassay screening, and the results were comparable to those of traditional liquid–liquid extraction (LLE). The method was solvent-saved, simple, rapid and reliable, and the extract was cleaner than that of LLE.

Synthesis markers in illegally manufactured 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine

In this paper the isolation and identification of 12 compounds as impurities in illicit 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) is reported. Isolation of these substances is performed by preparative TLC, while identification is performed by using mass spectrometry and 1H-NMR spectroscopy. A simple and rapid method for detection of these impurities in seized MDA and MDMA samples is described. The identification of the impurities can provide numerous points on which to base comparative analysis of different exhibits.

Detection of D,L-Amphetamine, D,L-Methamphetamine, and Illicit Amphetamine Analogs Using Diagnostic Products Corporation's Amphetamine and Methamphetamine Radioimmunoassay*

Cross-reactivity with Diagnostic Products Corporation (DPC) amphetamine and methamphetamine radioimmunoassay (RIA) reagents was determined for amphetamine, methamphetamine, and a number of amphetamine analogs. Concentrations from 100 to 100,000 ng/mL were assayed. 3,4-Methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) showed significant cross-reactivity for the amphetamine and methamphetamine reagents respectively. 4-Hydroxymethamphetamine, 3,4-methylenedioxyethylamphetamine (MDEA), and N,N-dimethyl-MDA also showed significant cross-reactivity with the methamphetamine reagents, but less than MDMA. None of the other analogs showed a positive result with the amphetamine or methamphetamine reagents at even the highest concentration, although several did show measurable cross-reactivity. The L isomers of amphetamine and methamphetamine showed substantially less cross-reactivity than the D forms to which the respective antibody systems are targeted.

Behavioral effects of (�) 3,4-methylenedioxyamphetamine (MDA) and (�) 3,4-methylenedioxymethamphetamine (MDMA) in the pigeon: interactions with noradrenergic and serotonergic systems

The effects of three amphetamine analogs were assessed in pigeons key pecking under a multiple 3-min fixed-interval (FI), 30 response fixed-ratio (FR) schedule of food presentation. At doses between 0.1 and 10.0 mg/kg, (+-) 3,4-methylenedioxyamphetamine (MDA), (+-) 3,4-methylenedioxymethamphetamine (MDMA), and (+-)-N-ethyl-3,4-methylenedioxyamphetamine (MDE) either had no effect or decreased response rates in both components of the multiple schedule in a dose-dependent manner. MDA was at least 1 log unit more potent than the other two compounds. Metergoline (0.1-1.0 mg/kg), a serotonin (5-HT) antagonist with comparable affinity for the 5-HT1 and 5-HT2 receptor subtypes, blocked the rate-decreasing effects of 3.0 mg/kg MDA in both components of the multiple schedule, but did not affect the MDMA dose-response curve. The 5-HT2 receptor antagonist ketanserin (0.1-3.0 mg/kg) also restored FI and FR responding that was decreased by 3.0 mg/kg MDA, but had no effect on responding suppressed by MDMA. The noradrenergic alpha-1 antagonist prazosin (0.3-3.0 mg/kg) blocked the behavioral effects of 3.0 mg/kg MDMA at doses that did not attenuate MDA's rate-decreasing effects. These results indicate that although MDA and MDMA are structurally similar and have similar behavioral effects, their actions appear to be mediated through different neurotransmitter systems.

Determination of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine enantiomers in whole blood.

A method for the determination of the enantiomeric content of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in microsamples (200 microliters) of whole blood is described. The method involves liquid-liquid extraction of MDA and MDMA from blood and derivatization with the chiral reagent N-trifluoroacetyl-L-prolyl chloride. Separation, identification and quantitation of diastereomeric derivatives is by gas chromatography-mass spectrometry. The analytical range of the assay is from 0.12 ng to 48 ng injected on-column. Details for the synthesis of the enantiomers of MDMA are also provided.

'Designer drugs'. A problem in clinical toxicology.

'Designer drugs' are substances intended for recreational use which are derivatives of approved drugs so as to circumvent existing legal restrictions. The term as popularised by the lay press lacks precision. Contrary to the popular belief that 'designer drugs' are original creations, the majority of these agents are 'borrowed' from legitimate pharmaceutical research. They merely represent the most recent developments in the evolution of mind-altering chemicals. The most extensively studied class of psychoactive compounds is the phenylethylamines (mescaline analogues). This class includes catecholamines, therapeutic agents and numerous illicit derivatives. Subtle alterations of the phenylethylamine molecule give rise to a spectrum of pharmacological properties ranging from pure sympathomimetic stimulation to primarily psychoactive effects. Although most of these compounds are only of historical interest, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) continue to be used recreationally. Many deaths have been ascribed to this class of compounds. In overdose the differences between these compounds blur and the clinical presentation is similar to that of amphetamine overdose characterised by tachycardia, hypertension, hyperthermia, diaphoresis, mydriasis, agitation, muscle rigidity, and hyper-reflexia. Death usually results from arrhythmias, hyperthermia or intracerebral haemorrhage. Treatment is aggressive and supportive with careful attention to temperature, blood pressure and seizure control. Synthetic opioid derivatives, which represent the second major class of 'designer drugs', are derivatives of fentanyl (e.g. alpha-methylfentanyl, 3-methylfentanyl) or pethidine (meperidine) and are extremely potent compounds responsible for numerous overdose deaths. Attempts to synthesise pethidine have resulted in the accidental production of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a compound which is metabolised in the brain by the monoamine oxidase system to a toxic intermediate (MPP+) which selectively destroys the sustantia nigra, resulting in the rapid onset of severe Parkinsonian symptoms. Naloxone will antagonise the opiate effects of this drug class, although high doses may be required. Arylhexylamines constitute the third class of 'designer drugs'. The predominant member of this class is phencyclidine (PCP), a derivative of the anaesthetic ketamine. This unique class of psychoactive agents exhibits broad and complex pharmacological effects.(ABSTRACT TRUNCATED AT 400 WORDS)