High-Throughput Screening of Drugs of Abuse in Urine by Supported Liquid–Liquid Extraction and UHPLC Coupled to Tandem MS

A qualitative method, involving supported liquid–liquid extraction (SLE) and ultra high pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS–MS), was developed for the rapid tentative identification of various drugs of abuse in urine. In this study, 28 drugs and metabolites were covered by the screening procedure. Before analysis, urine samples were extracted by SLE and good extraction recoveries were obtained for most investigated compounds. The UHPLC strategy was then selected for the rapid separation of amphetamines, cocaine, opiates and related compounds in urine. Using columns packed with sub-2 µm particles, analysis time was reduced down to 2 min, while maintaining acceptable performance. Finally, the detection was by tandem MS operating in the single reaction monitoring (SRM) mode. The most intense transition was selected for the different drugs and SRM dwell times set at 5 ms, to maintain sufficient data points across the narrow UHPLC peaks. The tentative identification of the drugs of interest, including amphetamines, opiates and cocaine, was based on both, retention times and mass spectrometry information. With the proposed method, limits of detection were estimated at about 1 ng mL^?1 and the applicability was assessed by successfully analyzing several samples of drug abusers. Finally, this study demonstrates the potential of UHPLC coupled to tandem MS for the rapid screening of drugs of abuse in urine.     

Two-dimensional liquid chromatography–ion trap mass spectrometry for the simultaneous determination of ketorolac enantiomers and paracetamol in human plasma: Application to a pharmacokinetic study

A bioanalytical method was developed for the simultaneous determination of paracetamol and ketorolac enantiomers in human plasma using two-dimensional liquid chromatography–mass spectrometry. Separation was first achieved in a reversed-phase C18 column by using a gradient solvent system consisting of 0.1% aqueous formic acid and acetonitrile (ACN). The effluent between 8.9 and 9.9 min, corresponding to phenacetin and racemic ketorolac peaks, was transferred to a polysaccharide-based chiral column (ChiralPak AD-RH) by using a six-port switching valve. Ketorolac enantiomers were subsequently separated on the chiral column using an isocratic mobile phase composed of ACN/0.1% formic acid 50:50 (v/v). The total run-time was less than 18 min. This innovative strategy prolongs the lifetime of chiral columns by avoiding damages due to the sample matrix. The detection was carried out with an ion trap mass spectrometer equipped with an electrospray ionisation source. The tested ranges were 0.05–20 μg/ml for paracetamol and 0.005–2 μg/ml for each ketorolac enantiomer. This method was fully validated and showed good performances in terms of trueness (80–110%) and precision (6.7–13.2%). The mean extraction recoveries were 60%, 72% and 76% for paracetamol, R-ketorolac and S-ketorolac, respectively. Finally, this procedure was successfully applied to a pharmacokinetic study.     

Investigation of structural and electronic properties of β- HgS: Molecular dynamics simulations

The pressure induced phase transition of β-HgS is studied using an ab initio molecular dynamics simulation. The structural phase transformation from the zinc-blende structure to the NaCl-type structure (space group $Fm\overline{3}m$) and from this structure to CsCl-type structure ($Pm\overline{3}m$) with the application of hydrostatic pressure is predicted. Additionally, the electronic properties of HgS and various physical properties such as the lattice constants, the bulk modulus and the pressure derivative of the bulk modulus are revealed. Furthermore, these phase transitions are obtained using the total energy and enthalpy calculations. According to these calculations these transformations are occurring at about 20?GPa and 28?GPa for $F\overline{4}3m$ →$Fm\overline{3}m$ and $Fm\overline{3}m$ →$Pm\overline{3}m$, respectively.     

Experimental design for enantioselective separation of celiprolol by capillary electrophoresis using sulfated beta-cyclodextrin

A capillary zone electrophoresis method was developed for the enantioseparation of celiprolol enantiomers, using a sulfated beta-cyclodextrin (beta-CD) as a chiral selector. The use of a coated capillary was necessary to achieve stable and reproducible enantioseparations. A central composite design was applied to optimize the method and four parameters were selected for this study: the buffer pH, the buffer concentration, the sulfated beta-CD concentration and the temperature. Resolution between celiprolol enantiomers as well as analysis time and generated current were established as responses. For each response, a model was obtained by a second-degree mathematical expression. From the models, the most favorable conditions were determined by optimizing the resolution between celiprolol enantiomers and by setting the two other responses at threshold values. Response surfaces were also used to assess the robustness of the analytical method around the optimal region. Successful results were obtained with a 52 mM acetate buffer at pH 4.0 in the presence of 3.0 mM sulfated beta-CD at a temperature of 19.5 degrees C. Under these optimized conditions, baseline separation of the celiprolol enantiomers was achieved in less than 10 min. The method showed good validation data in terms of precision, accuracy and linearity, and was found to be suitable in determining celiprolol enantiomers in pharmaceutical preparations and in biological fluids.     

Validation of capillary electrophoresis--mass spectrometry methods for the analysis of a pharmaceutical formulation

The coupling of capillary electrophoresis (CE) to mass spectrometry (MS) with an electrospray ionization (ESI) technique is generally performed for qualitative applications, and only few quantitative results have been reported. This paper investigates the validation of a CE-ESI-MS method for the analysis of a pharmaceutical formulation containing lidocaine. Some important ESI criteria are discussed including sheath-liquid composition, nebulizing gas pressure and position of the CE capillary outlet. After optimization of these parameters, an intermediate precision of about 5% was achieved. The latter, as well as efficiency and resolution, were compared to those achieved with UV detection. Besides, a multiple injection procedure was developed to reduce analysis time per sample and was successfully applied to both UV and MS detectors. The validation results achieved by multiple injections were identical to those obtained with classical injection, but afforded a gain of time by a factor of 2.5.     

Determination of the stability of caseinoglycomacropeptide in a cosmetic lotion by use of capillary zone electrophoresis with a coated capillary

Summary A capillary zone electrophoretic method is described for the determination of a caseinoglycomacropeptide. The optimized conditions employed a poly(vinyl alcohol)-coated capillary and 50 mM phosphate buffer at pH 2.5 to enable baseline separation of several glycoforms. The method was validated and performance was good in terms of precision (both peak area and migration time), selectivity, linearity, and accuracy. The method was used to determine caseinoglycomacropeptide (2%w/w) in a cosmetic lotion. The validated method was finally used to monitor the stability of this caseinoglycomacropeptide in the cosmetic lotion over a period of four months.     

Optimization of fast CE analyses of ecstasy derivatives by use of experimental designs

Summary The separation by capillary electrophoresis of five ecstasy derivatives has been evaluated by means of experimental designs. A full-factorial design and a central composite design were employed to optimize the experimental conditions for a fast separation. With a conventional capillary (62.5 cm length) analytes were separated in less than 8 min. When the capillary length was reduced the analysis time decreased substantially. Comparisons were made between different procedures (e.g. working at a constant field or at constant voltage) and finally, a fast separation of five Ecstasy derivatives was achieved in 1 min.     

Post-Harvest Operations to Generate High-Quality Medicinal Cannabis Products: A Systemic Review

The traditional Cannabis plant as a medicinal crop has been explored for many thousands of years. The Cannabis industry is rapidly growing; therefore, optimising drying methods and producing high-quality medical products have been a hot topic in recent years. We systemically analysed the current literature and drew a critical summary of the drying methods implemented thus far to preserve the quality of bioactive compounds from medicinal Cannabis. Different drying techniques have been one of the focal points during the post-harvesting operations, as drying preserves these Cannabis products with increased shelf life. We followed or even highlighted the most popular methods used. Drying methods have advanced from traditional hot air and oven drying methods to microwave-assisted hot air drying or freeze-drying. In this review, traditional and modern drying technologies are reviewed. Each technology will have different pros and cons of its own. Moreover, this review outlines the quality of the Cannabis plant component harvested plays a major role in drying efficiency and preserving the chemical constituents. The emergence of medical Cannabis, and cannabinoid research requires optimal post-harvesting processes for different Cannabis strains. We proposed the most suitable method for drying medicinal Cannabis to produce consistent, reliable and potent medicinal Cannabis. In addition, drying temperature, rate of drying, mode and storage conditions after drying influenced the Cannabis component retention and quality.     

Characterization and classification of matrix effects in biological samples analyses

An exhaustive classification of matrix effects occurring when a sample preparation is performed prior to liquid-chromatography coupled to mass spectrometry (LC–MS) analyses was proposed. A total of eight different situations were identified allowing the recognition of the matrix effect typology via the calculation of four recovery values. A set of 198 compounds was used to evaluate matrix effects after solid phase extraction (SPE) from plasma or urine samples prior to LC–ESI-MS analysis. Matrix effect identification was achieved for all compounds and classified through an organization chart. Only 17% of the tested compounds did not present significant matrix effects.