Impact of reaction parameters on the chemical profile of 3,4-methylenedioxymethamphetamine synthesized via reductive amination: target analysis based on GC-qMS compared to non-targeted analysis based on GC×GC-TOF-MS.

The most common clandestine manufacturing procedure for the ecstasy derivative 3,4-methylenedioxymethamphetamine (MDMA), is the reductive amination of piperonylmethylketone (PMK) via platinum(IV) oxide/hydrogen. Deviations of the reaction conditions during the synthesis may result in different chemical profiles of the products. The chemical analysis of these profiles is an important objective for forensic drug intelligence. In this work we studied the impact of a systematic variation of the hydrogenation time, the reaction temperature and the precursor batch on the resulting organic chemical profiles of the MDMA bases and MDMA hydrochlorides. Target analysis was based on a gas chromatography mass spectrometry (GC-MS) method which was harmonized during the European project CHAMP.(2) In addition, samples were analyzed by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS) and subjected to non-targeted data analysis for a comprehensive analysis of the complete profiles. The reaction temperature, followed by the used precursor batch, revealed the highest impact on the chemical profile. The effect on individual impurity compounds is discussed in detail. With respect to the interpretation of the data, the profiles were compared to the profiles of MDMA samples obtained by reductive amination using sodium borohydride ("cold method") and aluminium/mercury amalgam as alternative reducing agents. Non-targeted analysis revealed that the discrimination according to the synthetic route and the batch of precursor used for the synthesis strongly depends on the selected target compounds.

Determination of light-absorbing layers at inner capillary surface by cw excitation crossed-beam thermal-lens spectrometry.

A thermal-lens spectrometric unit suitable for selective quantitative measurements of light-absorbing layers adsorbed onto the inner surface of a quartz glass capillary is described. The quantitative description of the thermal-lens signal generated in a quartz glass capillary with a light-absorbing layer at the inner surface of capillary is developed, which is based on the description for the thermal-lens experiment in the layered solids presented elsewhere. The accuracy of calculations is demonstrated by the comparison of predicted results with the experimental data and those predicted by the conventional theory. The data achieved prove the accuracy of calculations both for the time dependent thermal-lens signal and for the lock-in amplifier signal under variation of the spectrometer configuration for capillaries having an adsorbed layer. The proposed technique is used for the investigation of chromate/2,10-ionene and 4-aminoazobenzene adsorption at capillary walls. The estimates of the minimum light absorption detectable at capillary walls are at a level of 1 x 10(-5) abs. units; the linear range of the thermal-lens signal from the inner surface layer no less than three orders of magnitude is predicted.

Indirect thermal lens detection for capillary electrophoresis.

Thermal lens detection with a 325.0nm He-Cd excitation laser is used for thermooptical indirect detection in combination with the capillary electrophoretic separation of organic anions. The optimization of indirect thermooptical detection is discussed. With Mordant Yellow 7 (an azo dye) chosen as a probe ion limits of detection for 1-heptane-, 1-pentane-, 1-butane-, 1-propanesulfonic, and acetic acid at a level of nx10(-7)M were achieved with a separation electrolyte containing 50muM of the probe ion and 5mM Tris pH 9.90. A further increase in the detection sensitivity (twofold decrease in the limit of detection ) was obtained with a separation electrolyte containing a volume fraction of 20% acetonitrile.

Investigation of ionene adsorption on quartz surfaces by thermal-lens spectrometry.

Thermal-lens spectrometry was used for the investigation of the adsorption of ionene to quartz surfaces. The thermooptical analysis of the surface makes it possible to distinguish the modified surface from a clean quartz surface and to provide sensitive direct concentration measurements of the light absorbing co-adsorbed substance. The co-adsorption of chromate ions and 2,10-ionene from aqueous solutions to quartz surfaces was investigated and the desorption procedure proposed.

Capillary electrochromatography with polymeric continuous beds synthesized via free radical polymerization in aqueous media using derivatized cyclodextrins as solubilizing agents.

A novel synthetic route to amphiphilic acrylamide-based monolithic stationary phases for capillary electrochromatography (CEC) employing water-soluble cyclodextrins as solubilizing agents was explored. N,N'-Octamethylenebisacryamide and N,N'-dodecamethylenebisacryamide were synthesized and their solubilization in aqueous solution with derivatized and underivatized cyclodextrins of different cavity size was studied. Amphiphilic stationary phases were synthesized by free radical copolymerization of the bisacrylamide-cyclodextrin host-guest complexes with hydrophilic monomers and an additional hydrophilic cross-linker in aqueous solution. Complex formation in solution and removal of the complexed cyclodextrin from the polymer during synthesis was studied with 1H-NMR and solid state 13C-NMR spectroscopy and cyclodextrin-modified micellar electrokinetic chromatography. The impact of the incorporated alkylene groups in the acrylamide-based macroporous polymer on retention was studied with neutral solutes by CEC in the normal-phase elution mode and in the reversed-phase elution mode. Batch-to-batch reproducibility of the synthesis procedure and day-to-day repeatability of the separations achieved were investigated. With these capillaries, a sufficiently high electroosmotic flow velocity, a high reproducibility and repeatability of separation parameters and high plate numbers (up to 200,000 m(-1) were obtained.

Polyrotaxane approach for synthesis of continuous beds for capillary electrochromatography.

The polyrotaxane formation approach was evaluated for synthesis of continuous beds for capillary electrochromatography. This approach has the advantage of generating diverse electroosmotic and chromatographic properties without chemical reactions. The polyrotaxane derivatized continuous beds were formed adding the macrocyclic compounds to the solution of neutral acrylic monomers and crosslinker prior to the initiation of the polymerisation. Cationic and anionic derivatives of beta-cyclodextrin were used as macrocyclic compounds. Investigation of the electroosmotic properties indicated a template directed and enthalpy controlled self-assembly of the polyrotaxanes during the polymerisation of the continuous beds. This process was monomer-composition dependent and favored by the hydrophobicity of the polymeric skeleton. The morphology of the continuous beds was evaluated using high-resolution optical microscopy with CCD camera and atomic force microscopy. Reversed-phase capillary chromatography driven by electroosmosis, originating from the polyrotaxane structure, was performed using several test mixtures. Not primarily designed for the chiral chromatography the polyrotaxane derivatized continuous beds demonstrated enantioselective separation of D,L-metoprolol. The stability of the polyrotaxane derivatized continuous beds was tested. The beds demonstrated reproducible electroosmotic properties in the range from pH 4 to pH 9 (RSD=0.69%).

Synthesis and characterization of polyrotaxane-based polymeric continuous beds for capillary electrochromatography.

The continuous bed technique with its attractive features, such as fritless design, one-step in situ synthesis, low back pressure and no need for pressurising the electrode vessels to suppress bubble formation was applied to form polyrotaxane-based stationary phases for capillary electrochromatography (CEC). Rotaxanes are synthesized from two classes of substances, namely linear reactive monomers and inert cyclic compounds. Upon polymerisation, a gel forms with the cyclic molecules mechanically immobilized (see Fig. 1). We have employed this simple approach, using charged derivatives of cyclodextrins in order to introduce charged groups into continuous beds and thus render them appropriate for electrochromatography. The self-assembly of supramolecular structures to form rotaxanes during the synthesis of the continuous beds is treated. The electroosmotic and chromatographic properties of the various polyrotaxane-based stationary phases synthesized are discussed, as well as the synthesis of the continuous beds, including how to affect their porosity and its influence on the efficiency of the electrokinetic separation. The applicability of the rotaxane-based continuous bed is demonstrated by separation of model compounds by reversed- and normal-phase chromatography. A separation of enantiomers is also presented. This experiment is of particular interest because it indicates that the interaction with the cavity of beta-cyclodextrin (beta-CD) is not a fundamental requirement for enantioseparations.

Micellar electrokinetic chromatography--from theoretical concepts to real samples (review).

Micellar electrokinetic chromatography (MEKC) is an alternative to liquid chromatographic separations. It is a highly efficient separation technique that is performed with the same experimental set-up as is used for capillary electrophoresis (CE), thus extending the applicability of CE to neutral solutes. MEKC can be regarded as a separation technique with a similar scope to that of reversed-phase high-performance liquid chromatography (RP-HPLC), having advantages over HPLC with regard to the efficiency of the separation system, separation speed, cost, and tolerance to matrix constituents. This paper discusses the applicability of MEKC to real samples and also addresses developments widening the scope of this emerging technique: on-line concentration by stacking or sweeping and sensitive detection schemes.

Advances in column technology and instrumentation in capillary electrochromatography.

Capillary electrochromatography (CEC) is an emerging technique gaining increased interest. Improvement of instrumentation and column technology will be of prime importance for the further development of this technique and its use in validated methods. In this paper, developments in column technology and instrumentation for CEC are reviewed with emphasis on developments within the last 3 years. Attention is directed to the employment of stationary phases specifically designed for CEC, the use of soft and rigid gels in place of packings, fritless packed capillaries, column dimensions, the optimization of injection and detection parameters, and gradient elution CEC.

Some considerations concerning the composition of the mobile phase in capillary electrochromatography.

In capillary electrochromatography (CEC) the propulsion of the mobile phase is effected by electroosmosis. The velocity of the electroosmotic flow is dependent on surface properties of the stationary phase and on bulk properties of the mobile phase. Therefore, in CEC the optimization of the mobile phase composition must take more factors into account than in pressure-driven LC. In this paper, the impact of the electrolyte concentration in the mobile phase and of the volume fraction of the organic mobile phase constituent on the velocity of the electroosmotic flow and on the chromatographic efficiency is investigated for CEC with capillaries packed with octadecylsilica gel. Bias of the data by an open section of the capillary has been excluded by employing completely packed capillaries and detection in a packed section. Acetonitrile as organic constituent of the mobile phase is compared to other possible organic modifiers (polar organic solvents) concerning influence on velocity of the electroosmotic flow and retention of solutes.

Widening of the elution window in micellar electrokinetic chromatography with cationic surfactants. II. Cationic additives and modifiers of the electroosmotic flow.

In micellar electrokinetic chromatography (MEKC) with cationic surfactants the migration window is significantly narrower than with anionic surfactants. In order to overcome this disadvantage of cationic surfactants, it is investigated whether it is possible to widen the migration window by reducing the velocity of the aqueous phase while the electrophoretic mobility of the micelles is maintained. Short chain alkylammonium compounds, hexamethonium bromide and hydroxypropylmethylcellulose are tested as additives to the separation electrolyte with the potential to improve the migration window via reducing the velocity of the electroosmotic flow. It will be shown that these modifiers can be successfully used in order to widen the migration window in MEKC with cationic surfactant employing an alkyltrimethylammonium bromide as micelle forming agents. Influence of the modifiers selected on retention of neutral and acidic solutes and on efficiency of the separation system is investigated.