Methamphetamine detection using portable capillary electrophoresis coupled with a swab-based extraction device.

Methamphetamine (MA) is one of the most virulent illicit drugs that can be synthesized from household materials leading to its prevalent trafficking and local manufacturing in clandestine drug laboratories (clan labs). The significant problems of tracing MA in clan labs and monitoring drug abusers lie in the lag time between sample collection and analysis and the number of tests done. Capillary electrophoresis (CE) is a rapid separation technique amenable to miniaturization and field testing. Herein, we developed a simple transient isotachophoretic (tITP)-CE method to detect MA and its precursor pseudoephedrine (PSE) in clan labs and non-invasive biological fluids. The method was implemented on the ETD-100, a commercial fully automated portable CE instrument with an integrated swab-based extraction system. Within 2 min of insertion of the swab, MA and PSE were automatically extracted with a leading electrolyte (LE) and then separated on covalently modified capillaries. The ETD-100 showed a limit of detection (LOD) and quantification (LOQ) of MA 0.02 and 0.05 µg/swab and 0.02 and 0.06 µg/swab of PSE, with an enhancement factor of 118 and 328, respectively, when compared to a normal non-tITP injection. The intra and inter-day relative standard deviation in terms of migration time were in the range of 0.75-1.93 % for both MA and PSE and were 2.0-2.4 % for both MA and PSE peak height. The method was demonstrated with the detection of spiked MA and PSE on different household materials as well as in non-invasive biological fluids with a recovery above 60 %.

Amino acid bound surfactants: a new synthetic family of polymeric monoliths opening up possibilities for chiral separations in capillary electrochromatography.

By combining a novel chiral amino-acid surfactant containing an acryloyl amide tail, a carbamate linker, and a leucine headgroup of different chain lengths with a conventional cross-linker and a polymerization technique, a new "one-pot" synthesis for the generation of amino-acid based polymeric monolith is realized. The method promises to open up the discovery of an amino-acid based polymeric monolith for chiral separations in capillary electrochromatography (CEC). The possibility of enhanced chemoselectivity for simultaneous separation of ephedrine and pseudoephedrine containing multiple chiral centers and the potential use of this amino-acid surfactant bound column for CEC and CEC coupled to mass spectrometric detection are demonstrated.

Chemical constituents of the stems of Ephedra sinica.

A new naphthalene derivative, 1-methyl-2,3-methylenedioxy-6-naphthalenecarboxylic acid methyl ester (1), and a new alkaloid, ( +/- )-1-phenyl-2-imido-1-propanol (2), together with the four known compounds, ephedrine, pseudoephedrine, N-methylephedrine, and 6-methoxykynurenic acid, have been isolated from the stems of Ephedra sinica, a famous traditional Chinese herbal medicine. The structures of 1 and 2 were determined by spectroscopic methods, including 1D- and 2D-NMR experiments as well as HR-EI-MS analysis.

[The Adverse Effects of Ephedra Herb and the Safety of Ephedrine Alkaloids-free Ephedra Herb Extract (EFE)].

Ephedra Herb is defined in the 17th edition of the Japanese Pharmacopoeia (JP) as the terrestrial stem of Ephedra sinica Stapf., Ephedra intermedia Schrenk et C.A. Meyer, or Ephedra equisetina Bunge (Ephedraceae). The stems of Ephedra Herb contain greater than 0.7% ephedrine alkaloids (ephedrine and pseudoephedrine). Despite its high effectiveness, Ephedra Herb exert several adverse effects, including palpitation, excitation, insomnia, and dysuria. Both the primary and adverse effects of Ephedra Herb have been traditionally believed to be mediated by these ephedrine alkaloids. However, our study found that several pharmacological actions of Ephedra Herb were not associated with ephedrine alkaloids. We prepared an ephedrine alkaloid-free Ephedra Herb extract (EFE) by eliminating ephedrine alkaloids from Ephedra Herb extract (EHE) using ion-exchange column chromatography. EFE exerted analgesic, anti-influenza, and anticancer activities in the same manner as EHE. Moreover, EFE did not induce adverse effects due to ephedrine alkaloids, such as excitation, insomnia, and arrhythmias, and showed no toxicity. Furthermore, we evaluated the safety of EFE in healthy volunteers. The number of adverse event cases was higher in the EHE-treated group than in the EFE-treated group, although the difference was not significant. Our evidence suggested that EFE was safer than EHE.

[Determination of the synthetic route based on impurity profiling of methamphetamine].

OBJECTIVE: Impurity profiling of seized methamphetamine may play an important role in the determination of the synthetic method employed and the criminal investigations of drug traffic routes. METHODS: A sample of methamphetamine was dissolved in buffer solution. Impurities were extracted with ethyl acetate containing four internal standards (n-decane, n-pentadecane, n-eicosane and n-octacosane) and analyzed by GC-MS. RESULTS: These data are suggestive of ephedrine/pseudoephedrine as the main precursor of the methamphetamine samples seized during 2006-2007. Six samples of selected eight samples were synthesized via the more specific ephedrine/hydriodic acid/red phosphorus method. CONCLUSION: Ephedrine/pseudoephedrine is common material used to synthesize methamphetamine.

Magnetic nano graphene oxide as solid phase extraction adsorbent coupled with liquid chromatography to determine pseudoephedrine in urine samples.

This paper reports on a method based on magnetic solid phase extraction (MSPE) for the determination of pseudoephedrine. Magnetic nanographene oxide (MNGO) was applied as a new adsorbent for the extraction of pseudoephedrine from urine samples. Synthesis of MNGO was characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). The main factors influencing extraction efficiency, including the amounts of sample volume, amount of adsorbent, type and amount of extraction organic solvent, time of extraction and desorption, pH, ionic strength of extraction medium, and agitation rate, were investigated and optimized. Under optimized extraction conditions, a good linearity was observed in the range of 100-2000ng/mL with a correlation coefficient of 0.9908 (r(2)). Limit of detection (LOD) and limit of quantification (LOQ) were 25 and 82.7ng/mL, respectively. Inter-day and intra-day precision and accuracy were 6.01 and 0.34 (%), and 8.70 and 0.29 (%), respectively. The method was applied for the determination of pseudoephedrine in urine samples of volunteers receiving pseudoephedrine with the recovery of 96.42. It was concluded that the proposed method can be applied in diagnostic clinics.

Capillary gas chromatography using a γ-cyclodextrin for enantiomeric separation of methylamphetamine, its precursors and chloro intermediates after optimization of the derivatization reaction.

The enantiomeric ratio of methylamphetamine (MAMP) is closely related to the optical activity of precursors and reagents used for the synthesis and this knowledge can provide useful information concerning the origins and synthetic methods used for illicit manufacture. The information can be utilized for regulation of the precursors and investigation of the manufacturing sources but this requires analytical procedures to determine purity of drug substances, impurity profiling and enantiomeric composition. In this study, a gas chromatography (GC) coupled with mass spectrometry (MS) method using a γ-cyclodextrin chiral stationary phase was developed and optimized for the simultaneous enantiomeric separations of MAMP and its common precursors, ephedrine, and pseudoephedrine, as well as its chlorointermediates formed during MAMP synthesis by the Emde method, after derivatization with trifluoroacetic anhydride. The optimization was performed using multivariate statistics (cluster analysis and principal components analysis) in order to select and compare optimal experimental conditions. Under the optimized experimental conditions, the calculated calibration curves showed good linearity range up to 0.1µg/mL for all tested analytes. The limits of detection were in the range of 0.002-0.008µg/mL and the coefficient of variability was between 1.0 and 3.9%. The method has the advantage of achieving excellent precision under repeatability and reproducibility conditions while detection by MS allows for the identity of analytes to be confirmed in a single analysis. The method was therefore applied satisfactory to MAMP analysis.

Monolithic molecular imprinted polymer fiber for recognition and solid phase microextraction of ephedrine and pseudoephedrine in biological samples prior to capillary electrophoresis analysis.

A novel capillary electrophoresis (CE) method coupled with monolithic molecular imprinted polymer (MIP) fiber based solid phase microextraction (SPME) was developed for selective and sensitive determination of ephedrine (E) and pseudoephedrine (PE). With in situ polymerization in a silica capillary mold and E as template, the MIP fibers could be produced in batch reproducibly and each fiber was available for 50 extraction cycles without significant decrease in extraction ability. Using the MIP fiber under optimized extraction conditions, CE detection limits of E and PE were greatly lowered from 0.20 to 0.00096 µg/mL and 0.12 to 0.0011 µg/mL, respectively. Analysis of urine and serum samples by the MIP-SPME-CE method was also performed, with results indicating that E and PE could be selectively extracted. The recoveries and relative standard deviations (RSDs) for sample analysis were found in the range of 91-104% and 3.8-9.1%, respectively.

Application of experimental design in optimization of the separation condition for determination of four active components in cold medicines by flow injection-capillary electrophoresis.

Orthogonal design (OD) was employed to optimize the separation condition of flow injection-capillary electrophoresis (FI-CE). In order to compare the optimum condition, uniform design and univariate approach were also adopted. The influences of variables such as buffer pH, buffer concentration, acetonitrile (ACN) percentage, and separation voltage were discussed. The optimum separation condition was established. The limits of detection were 1.94 × 10(-2), 6.40 × 10(-3), 1.16 × 10(-2) and 1.94 × 10(-2) µg/mL for dextromethorphan hydrobromide (Dex), chlorphenamine hydrogen maleate (Chl), pseudoephedrine hydrochloride (Pse), and paracetamol (Par), respectively. The RSDs of peaks areas were less than 2.0%. The results showed the OD was an effective method among experimental designs for optimizing the separation conditions of CE. The optimum condition was used for separation and determination of Dex, Chl, Pse, and Par in cold medicines. The average recovery was between 96.68-101.25%.

Studies of Ephedra plants in Asia. Part 6: Geographical changes of anatomical features and alkaloids content of Ephedra sinica.

Ephedra sinica Stapf is the main botanical origin of the Chinese herbal drug Mahuang, Ephedra Herb. Eighty-five samples of E. sinica, collected across eastern China, Mongolia, and Buryatia (Russia), were studied anatomically and chemically to elucidate the local variations and the relation between environmental factors and the variations. The results showed that samples grown in more arid conditions tended to have a more sinuous epidermis, more cuticular tubers, and more subepidermal fiber bundles anatomically, and contained more total ephedrine alkaloids. These samples also had a high pseudoephedrine content. These results imply that Ephedra Herb with good quality should be collected from arid fields, and the chemical quality can be estimated by observing the anatomical characteristics.

Recoveries of trace pseudoephedrine and methamphetamine residues from impermeable household surfaces: implications for sampling methods used during remediation of clandestine methamphetamine laboratories.

Evaluation of the risk posed by contaminants present during and after decontamination of clandestine methamphetamine laboratories requires a connection between the levels of contaminants measured and those actually present at the scene. The recoveries of pseudoephedrine and methamphetamine from glass, stainless steel, and a range of impermeable surfaces likely to be found in a clandestine laboratory were examined, using GC-MS of derivatized samples as the analytical method. When surfaces had been cleaned prior to drug deposition, wiping with water-dampened filter paper can recover 60-80% of pseudoephedrine immediately after deposition, and at least 50% of the pseudoephedrine still present on a surface after 2 days when deposited at a surface concentration of 2.5 microg/100 cm(2). Wiping with methanol-dampened filter paper could recover 60-90% of the methamphetamine immediately after deposition, and could recover at least 50-60% of the methamphetamine still present after 2 days when 0.6 microg/100 cm(2) was initially deposited on the surface. Recoveries were lower for surfaces that had not been pre-cleaned. Methamphetamine and pseudoephedrine showed significant volatility in both the free base and hydrochloride forms, with experiments in an enclosed format showing up to half the recovered drug being present on a glass plate held about 4mm above a substrate contaminated with one of the drugs at the above surface concentrations after 2 days. It is therefore important to remove any visible bulk contaminants and remove obvious pseudoephedrine or methamphetamine-contaminated surfaces prior to heating, ventilation or sealing of a clandestine laboratory to avoid redistribution of material around the site. A revised method for pseudoephedrine analysis was developed that could also detect the pseudoephedrine-formaldehyde adduct that can form from trace pseudoephedrine present at clandestine laboratories.

Effect of microemulsion component purity on the chromatographic figures of merit in chiral microemulsion electrokinetic chromatography.

Numerous combinations of one-, two-, and three-chiral-component microemulsions have been previously prepared in our group, using N-dodecoxycarbonylvaline (DDCV), 2-hexanol, and ethyl acetate, dibutyl tartrate, or diethyl tartrate. A few results of the various formulations investigated suggested the possible presence of minor impurities in one or more components of the microemulsion. In this study, the purity of the current lots of R- and S-surfactant were measured, as was the subsequent effect of minor impurities on the relevant chromatographic figures of merit (CFOMs) that describe a chiral separation, i.e., efficiency, enantioselectivity, retention, migration window (elution range), and resolution. Two related methods are proposed for correcting enantioselectivities measured in the presence of chiral impurities in the chiral microemulsion.

Separation and determination of ephedrine and pseudoephedrine in Ephedrae Herba by CZE modified with a Cu(II)-L-lysine complex.

A CZE method using a complex of 2.5 mM Cu(II)-L-lysine (molar ratio is 1:2) as additive in a run buffer solution composed of Tris-H(3)PO(4) (pH 4.5) was developed for the simultaneous determination of ephedrine and pseudoephedrine within 4 min. The effects of pH, composition, and concentration of run buffer as well as the composition and concentration of the Cu(II)-L-lysine complex on the separation were investigated. The linear ranges for the determination of ephedrine and pseudoephedrine were 15.0-225.0 and 20.0-250.0 mg/L with LODs both of 5.0 mg/L. Satisfactory result for the determination of ephedrine and pseudoephedrine in Ephedrae Herba from different producing area was obtained by the proposed method. Ephedrine and pseudoephedrine were separated effectively with each other and with the other compounds in the sample. The RSD for the determination of the two constituents in the samples varied from 1.82 to 2.76%, and the recovery ranged between 95.0 and 104.0%.