Capillary electrophoresis in clinical and forensic analysis: recent advances and breakthrough to routine applications

This paper is a comprehensive review article on capillary electrophoresis (CE) in clinical and forensic analysis. It is based upon the literature of 1997 and 1998, presents CE examples in major fields of application, and provides an overview of the key achievements encountered, including those associated with the analysis of drugs, serum proteins, hemoglobin variants, and nucleic acids. For CE in clinical and forensic analysis, the past two years witnessed a breakthrough to routine applications. As most coauthors of this review are associated with diagnostic or forensic laboratories now using CE on a routine basis, this review also contains data from routine applications in drug, protein, and DNA analysis. With the first-hand experience of providing analytical service under stringent quality control conditions, aspects of quality assurance, assay specifications for clinical and forensic CE and the pros and cons of this maturing, cost-and pollution-controlled age technology are also discussed.     

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.     

On simply laced Lie algebras and their minuscule representations

In this paper we adapt a known construction for the simply laced, semisimple Lie algebras (over Z), and thereby obtain a very simple construction for all minuscule representations of those Lie algebras (again over Z). We apply these results to give explicit formulas for tensors invariant under the exceptional algebras and . Received: November 3, 2000     

Low Field (10 mT) Pulsed Dynamic Nuclear Polarization

EPR irradiation by a train of inverting pulses has potential advantages over continuous-wave EPR irradiation in DNP applications; however, it has previously been used only at high field (5 T). This paper presents the design and testing of an apparatus for performing pulsed DNP experiments at 10 mT with large samples (17 ml). Experimental results using pulsed DNP with an aqueous solution of a narrow-linewidth paramagnetic probe are presented. A maximum DNP enhancement of about -36 with a train of inverting pulses (width 500 ns, repetition time 4 micros) was measured. A preliminary comparison showed that, when the same enhancement value is considered, the pulsed DNP technique requires an average power that is about three times higher than that required with the CW irradiation. However, for in vivo DNP applications it is very important to minimize the average power deposited in the sample. From the experimental results reported in this work, when considering the maximum enhancement, the pulsed technique requires only 2% of the average power necessary with the CW DNP technique. We believe that this reduction in the average power can be important for future DNP studies with large biological samples.     

Ideal nonsymmetric 4D-medium as a model of invertible dynamic thermoelasticity

The space-time continuum (4D-medium) is considered, and a generalized model of reversible dynamic thermoelasticity is constructed as a theory of elasticity of an ideal (defect-free) nonsymmetric 4D-medium that is transversally-isotropic with respect to the time coordinate. The definitions of stresses and strains for the space-time continuum are introduced. The constitutive equations of the medium model relating the components of nonsymmetric stress and distortion 4D-tensors are stated. Physical interpretations of all tensor components of the thermomechanical properties are given. The Lagrangian of the generalized model of coupled dynamic thermoelasticity is presented, and the Euler equations are analyzed. It is shown that the three Euler equations are generalized equations of motion of the dynamic classical thermoelasticity, and the last, fourth, equation is a generalized heat equation which allows one to predict the wave properties of heat. An energy-consistent version of thermoelasticity is constructed where the Duhamel-Neumann and Maxwell-Cattaneo laws (a nonclassical generalization of the Fourier law for the heat flow) are direct consequences of the constitutive equations.     

On the Generalized Heat Conduction Laws in the Reversible Thermodynamics of a Continuous Medium

Doklady Physics - A general covariance variational model of reversible thermodynamics is developed in which the kinematic and force variables are the components of unified tensor objects in the...     

On correct nonlocal generalized theories of elasticity

The paper discusses nonlocal elasticity theories among which are models of media with defect fields, gradient elasticity theories, and hybrid nonlocal elasticity theories. Gradient theories are analyzed, and their correctness properties are examined. Applied theories that satisfy the correctness conditions are developed, and known applied gradient theories are verified for the correctness properties. A new nonlocal generalized theory has been developed for which the operator of balance equations is represented as the product of the equilibrium operator of classical elasticity theory and the Helmholtz operator. It is shown that this theory is one-parameter and is the only representative of hybrid models constructed by a complete system of equations for forces and moments. Unlike classical elasticity that is free from scale parameters characterizing the internal material structure, nonlocal elasticity theories naturally incorporate these parameters. That is why they are suitable for the modeling of scale effects and find application in the solution of numerous applied problems for heterogeneous structures with developed phase interfaces where the degree of influence of scale effects depends on the density of phase boundaries. Nonlocal continuum models are especially attractive for modeling the properties of various micro/nanostructures, elastic properties of composites and structured materials with submicron- and nanosized internal structures in which effective properties are to a great extent defined by the scale effects (short-range interaction effects of cohesion and adhesion). Generalized elasticity theories even for isotropic materials contain many additional physical constants that are difficult or impossible to determine experimentally. Applied models with a small number of additional physical parameters are therefore of great interest. However, the reduction of nonlocal theories aimed at reducing the number of additional parameters is a nontrivial task and may lead to incorrect theories. The goal of this paper is to study the symmetry properties in gradient theories, to analyze the correctness of gradient theories, and to develop applied one-parameter elasticity theories.     

Use of multiple-reaction monitoring ratios for identifying incompletely resolved fentanyl homologs and analogs via ultra-high-pressure liquid chromatography–tandem mass spectrometry

Fentanyl and 16 of its corresponding homologs and analogs were distinguished using ultra-high-pressure liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). A 1.7 μm Acquity BEH C18 column (150 mm × 2.1 mm) was used with a 1% formic acid (pH 2.2), methanol gradient. Multiple-reaction monitoring (MRM) was employed for MS/MS detection. All selected fentanyl-related compounds, including incompletely resolved compounds, were uniquely identified using retention times and dual MRMs.     

Real-time monitoring of drug-induced changes in the stomach acidity of living rats using improved pH-sensitive nitroxides and low-field EPR techniques

New improved pH-sensitive nitroxides were applied for in vivo studies. An increased stability of the probes towards reduction was achieved by the introduction of the bulky ethyl groups in the vicinity of the paramagnetic NO fragment. In addition, the range of pH sensitivity of the approach was extended by the synthesis of probes with two ionizable groups, and, therefore, with two pKa values. Stability towards reduction and spectral characteristics of the three new probes were determined in vitro using 290 MHz radiofrequency (RF)- and X-band electron paramagnetic resonance (EPR), longitudinally detected EPR (LODEPR), and field-cycled dynamic nuclear polarization (FC-DNP) techniques. The newly synthesized probe, 4-[bis(2-hydroxyethyl)amino]-2-pyridine-4-yl-2,5,5-triethyl-2,5-dihydro-1H-imidazol-oxyl, was found to be the most appropriate for the application in the stomach due to both higher stability and convenient pH sensitivity range from pH 1.8 to 6. LODEPR, FC-DNP and proton-electron double resonance imaging (PEDRI) techniques were used to detect the nitroxide localization and acidity in the rat stomach. Improved probe characteristics allowed us to follow in vivo the drug-induced perturbation in the stomach acidity and its normalization afterwards during 1 h or longer period of time. The results show the applicability of the techniques for monitoring drug pharmacology and disease in the living animals.