Comprehensive two-dimensional gas chromatography applied to illicit drug analysis.

Multidimensional gas chromatography (MDGC), and especially its latest incarnation--comprehensive two-dimensional gas chromatography (GC × GC)--have proved advantageous over and above classic one-dimensional gas chromatography (1D GC) in many areas of analysis by offering improved peak capacity, often enhanced sensitivity and, especially in the case of GC × GC, the unique feature of 'structured' chromatograms. This article reviews recent advances in MDGC and GC × GC in drug analysis with special focus on ecstasy, heroin and cocaine profiling. Although 1D GC is still the method of choice for drug profiling in most laboratories because of its simplicity and instrument availability, GC × GC is a tempting proposition for this purpose because of its ability to generate a higher net information content. Effluent refocusing due to the modulation (compression) process, combined with the separation on two 'orthogonal' columns, results in more components being well resolved and therefore being analytically and statistically useful to the profile. The spread of the components in the two-dimensional plots is strongly dependent on the extent of retention 'orthogonality' (i.e. the extent to which the two phases possess different or independent retention mechanisms towards sample constituents) between the two columns. The benefits of 'information-driven' drug profiling, where more points of reference are usually required for sample differentiation, are discussed. In addition, several limitations in application of MDGC in drug profiling, including data acquisition rate, column temperature limit, column phase orthogonality and chiral separation, are considered and discussed. Although the review focuses on the articles published in the last decade, a brief chronological preview of the profiling methods used throughout the last three decades is given.

Disposable microfluidic device with ultraviolet detection for highly resolved screening of illicit drugs.

A disposable microfluidic device was constructed by conveniently integrating one poly(methyl methacrylate) board with four reservoirs and one fractured fused-silica capillary with 50 microm i.d. and 7.5 cm total length on a printed circuit board for applying sampling and separation voltages. The disposable microfluidic device combined with a home-made ultraviolet workstation could be conveniently used for efficient screening and quantitative detection of microg mL(-1) illicit drugs. Using eight illicit drugs as models, they could be baseline-separated within 240 s with the separation efficiency up to 600,047 plates m(-1) at the designed device. The novel device and proposed protocol were successfully used to screen illicit drugs in human urine. This work presented a simple and low-cost method to fabricate the microfluidic device and provided a powerful way for sensitive and specific multi-screening of different drugs with high resolution, fast separation and low-cost.

Applicability of ultra-performance liquid chromatography-tandem mass spectrometry for heroin profiling.

The applicability of ultra- performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) for heroin profiling is described. The coupling of the high separation power of UPLC with the highly selective and sensitive detection of MS/MS is well suited for heroin profiling. An Acquity UPLC BEH C18 1.7 microm particle column (100 mm x 2.1mm) with binary gradients containing 1% formic acid (pH 2.0) or 10 mM ammonium bicarbonate (pH 10.0)/acetonitrile mixtures was investigated for the profiling. For MS/MS detection, an atmospheric pressure positive electrospray source was employed with multiple reaction monitoring (MRM). MRMs for individual basic impurities were generated for heroin profiling using low and high pH mobile phases, while MRMs for neutral impurities were generated using a high pH mobile phase. Compared to a pH 2.2 mobile phase, the use of a pH 10 mobile phase allowed for significantly greater sample loading, major selectivity differences, and lower MRM sensitivity. UPLC-MS/MS allowed for the highly selective and sensitive detection of many of the targeted solutes in seized heroin exhibits. Basic impurities detected included morphine, codeine, noscapine, papaverine and the previously unreported solutes reticuline, reticuline monoacetate (2 products), reticuline diacetate, narceine, codamine, laudanidine, cryptopine, laudanosine, and norlaudanosine. Neutral impurities found included N,3,6-triacetylnormorphine, N-acetylnorcodeine, N-acetylnornarcotine, 3,6-dimethoxy-4-acetyloxy-5-[2-(N-methylacetamido)]-ethylphenanthrene, and cis-n-acetylanhydronornarceine. The detection of these impurities, at levels as low as 10(-6)% w/w should allow for greatly enhanced heroin profiles.

Preparation and evaluation of solid-phase microextraction fibers based on monolithic molecularly imprinted polymers for selective extraction of diacetylmorphine and analogous compounds.

All of the studies on solid-phase microextraction based on molecularly imprinted polymers up to now have been carried out on the synthesis of the polymer on the surface of the fiber which is brittle and the polymer coating strips during handling. The objective of this study was to develop a method for fabrication of a monolithic and robust solid-phase microextraction fiber on the basis of molecularly imprinted polymer for selective extraction of diacetylmorphine and its structural analogues followed by their GC or GC/MS analysis. A fiber was produced by copolymerization of methacrylic acid-ethylene glycol dimethacrylate imprinted with diacetylmorphine. The effective factors influencing the polymerization have been investigated and are detailed here. Also, the influences of pH, extraction time and temperature on the extraction efficiency of analytes were investigated. The prepared fiber was thermally stable up to 300 degrees C which has vital importance in SPME coupled with GC or GC/MS. The adsorption isotherm modeling was performed by fitting the data of studied compounds to bi-Langmuir isotherm model. The evaluated equilibrium constants for diacetylmorphine were 0.011 and 1824.72 microM(-1), and the number of binding sites was 170.37 and 4.64 nmolg(-1), respectively. This fiber was successfully used for extraction of template molecule from aqueous solution and further analysis with GC or GC/MS. The high extraction efficiency was obtained for diacetylmorphine, 6-monoacetylcodeine, and 6-monoacetylmorphine, yielding the detection limits of 300, 47, and 1 ngmL(-1), respectively.

Separation and detection of acidic and neutral impurities in illicit heroin via capillary electrophoresis.

The separation and detection of acidic and neutral impurities in illicit heroin using capillary electrophoresis (CE) is described. Separations were achieved using charged cyclodextrin modified micellar electrokinetic capillary chromatography. The use of the anionic beta-cyclodextrin sulfobutyl ether 1V in combination with sodium dodecyl sulfate significantly increased resolution. Improved selectivity and/or sensitivity in detection was obtained using photodiode array ultraviolet and laser-induced fluorescence detection. The phenanthrene-like heroin impurities exhibit high native fluorescence under krypton-fluoride laser excitation (248 nm). The limit of detection by laser-induced fluorescence detection for one of these solutes (acetylthebaol) is 1.8 ng/ml, 500 times more sensitive than UV. This methodology is applicable to analysis of both crude and refined heroin.

The separation and quantitation of the narcotic components of illicit heroin using reversed-phase high performance liquid chromatography.

The separation of heroin from other narcotic components of illicit preparations is achieved by high performance liquid chromatography. Using an aminopropyl bonded silica packing and a mixture of 85% acetonitrile and 15% 0.005 M tetrabutylammonium phosphate as the mobile phase, caffeine, heroin, acetylcodeine, 6-acetylmorphine, codeine, and morphine are separated from each other and are accurately quantified. Papaverine, noscapine, thebaine, and strychnine are also separated from these principal components.

Simple high-performance liquid chromatographic method for the separation of 3,6-diacetylmorphine hydrochloride (heroin) and hydrolysis products.

The application of reversed-phase high-performance liquid chromatography to the measurement of 3,6-diacetylmorphine (DAM) hydrochloride and its degradation products is described. This method has been applied to study the kinetics of the DAM hydrolysis at 26 +/- 0.1 degrees and 48 +/- 0.1 degrees. The hydrolysis of DAM involved a two-step first-order sequential mechanism between pH 3 and 8.6. The first-order rate constants of each step at all pH levels have been determined. The pH rate profile was constructed from kinetic measurements and demonstrated that stability of DAM hydrochloride solutions was optimal at pH 4.3. This information is being applied to the development of parenteral dosage forms of DAM hydrochloride.