This review article provides information on the development of liposomal drug delivery systems to cross the blood(brain barrier (BBB). Information on the use of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, for the prevention and treatment of Alzheimer’s disease is provided. Methods for modifying the surface of liposomes to ensure transport through the BBB are considered in detail. Various forms for intranasal administration of drugs to improve their passage through the BBB are also highlighted. The presented information allows us to conclude that it is expedient to develop an intranasal liposomal form of pioglitazone for the treatment and prevention of Alzheimer’s disease.
The work is devoted to the search for conditions for the sample preparation and determination of carbamazepine and oxcarbazepine and identification of the products of their metabolism and degradation in human liver (post mortem) and material evidences by gas chromatography–mass spectrometry. A QUECHERS approach was developed to the sample preparation of carbamazepine and oxcarbazepine. Amitriptyline was proposed as an internal standard. Degradation products of carbamazepine and oxcarbazepine were studied in model solutions upon alkaline and acid hydrolysis and oxidation; 14 metabolites and degradation products were identified. The main analytical characteristics of the developed procedure were determined. The limits of detection are 0.1 and 0.2 µg/g for carbamazepine and oxcarbazepine, respectively. The developed procedure complies with the Validation Guidelines of the Russian Center for Forensic Medical Examination.
Molecular mechanisms of development of normal and pathological neuroendocrine and immune adaptive response to psychological (mental) stress are analyzed considering its possible provoking role in the development of rheumatoid arthritis (RA). A detailed analysis reveals the synergism of mechanisms that provoke the development of pathological anti-stress adaptive response and RA. It is possible that in persons at risk of developing RA minimal and unobtrusive for the individual stressful situations, periodically provoking prolonged production of pro-inflammatory cytokines, can, finally, lead to the development of rheumatic disease.
A soot coating was treated with NO3 radicals using a flow reactor having a movable insert and coupled to a mass spectrometer for kinetic studies; the treatment was performed until the surface completely stopped to trap the radicals. The chromatographic and mass spectrometry analyses of the composition of the original methane soot and the solid products of its reaction with the gas-phase NO3 oxidant showed that the main products of this heterogeneous reaction were phthalic acid derivatives, paraffins, and acetophenones. The untreated soot contained arenes (up to four-membered aromatic molecules). The nitro compounds were not detected in the original soot and the products of its treatment with NO3 radicals.
This article is focused on the conditions for the detection and identification of 2-[4-bromo-2.5-dimethoxyl]-N-[(2-methoxyphenyl)methyl] ethamine (25B-NBOMe) and its major metabolites by the combination of the HPLC/MS/MS techniques. The high-resolution mass spectra obtained with the use of a linear ion trap are described. The results of the study give evidence of the possibility for the detection of the analytes within 24 hours after drug consumption and within 3 months after the storage of the biological material of interest in a refrigerator at a temperature of 3-5 °C. The data obtained confirmed high stability of 2-(4-bromo-2.5-dimethoxyl]-N-[(2-methoxyphenyl)methyl] ethamine and its metabolites in the biological tissues.
The objective of the present study was the development and validation of the rapid reproducible method for the identification of ethyl glucuronide and ethyl sulfate allowing to store and transport the study specimens without the loss of the substances of interest by placing the samples on the paper. We have developed the validated technique for the detection and quantitative determination of ethyl glucuronide and ethyl sulfate in the cadaveric blood and urine by means of low-resolution tandem mass-spectroscopy with the use of deuterated derivatives of these substances as the internal standards. The low threshold for quantitative determination of both above substances is 50 ng/ml for the blood and 100 ng/ml for the urine. The method is characterized by the accuracy and precision with the coefficient of variation below 15% and the influence of the matrix with the coefficient of variation below 15%. The evaluation of stability of the two analytes in blood when stored in the dry condition on the paper carrier during 2 weeks showed that the coefficient of variation did not exceed 6.4%. The comparative study of ethyl glucuronide and ethyl sulfate in the samples of cadaveric blood and urine containing from 0 to 5.2% of ethyl alcohol was carried out. The methods for the transportation of the biological fluids and for the extraction of ethyl glucuronide and ethyl sulfate placed on the paper carrier (Whatman 903) have been proposed. The possibility has been demonstrated to use ethyl glucuronide and ethyl sulfate as the markers of the consumption of ethyl alcohol during one's lifetime for the purpose of investigation of the putrifactive changes of the blood components.
The uptake of NO 3 on a pyrene coating at [NO 3 ] = 2.5 × 10 12 –1.2 × 10 13 cm −3 is studied using a coated-insert flow tube reactor coupled to a mass spectrometer. It is established that, in this concentration range, the uptake occurs by the impact recombination mechanism, whereas the consumption of surface sites involves the unimolecular decomposition of stabilized surface complexes. Several hundreds of NO 3 radicals are consumed per surface site destroyed. The uptake coefficient depends on the exposure time, being described by the expression γ( t ) = γ 0 exp(− t /τ), where γ 0 and τ are parameters dependent on the NO 3 concentration. Based on the Langmuir adsorption concept, the following elementary parameters determining the uptake process are estimated: the Langmuir coefficient, K L = 7.1 × 10 −13 cm 3 ; the desorption rate constant, k d = 44 s −1 ; and the rate constant for the unimolecular heterogeneous conversion of surface complexes, k r = 6.6 × 10 −2 s −1 . Gas chromatography–mass spectrometry measurements showed that the main products of the reaction are phthalates. The nitropyrene yield is found to be ~0.6%.
A technique of extracting cotinine in urine and wastewaters, followed by its quantitative determination, using high performance liquid chromatography combined with tandem mass-spectrometric detection is presented. The method is characterized by low detection limits and high levels of efficiency and sensitivity. The optimal conditions for the solid-phase extraction of cotinine from urine and wastewaters are found. This technique makes it possible to reliably estimate the content of cotinine in the urine of active and passive smokers and in wastewaters.
The consumption of JWH-018, an agonist of cannabinoid receptors within a number of smoking mixtures, can be established though the detection of its metabolites in human blood and urine. Using gas and liquid chromatography coupled with mass spectrometry, we identified 14 metabolites of JWH-018, products of mono- and dihydroxylation of aromatic and aliphatic moieties in the initial structure, carboxylation, dealkylation, and dealkylation followed by hydroxylation processes, in human and rat urine. The predominant metabolites excreted with urine, which can also be detected in human blood serum, were found to be products of monohydroxylation and in urine of rats, products of dealkylation with monohydroxylation.
The authors suggest a simple sensitive technique for enzyme immunoassay (EIA) of ABH antigens in saliva and semen. A two-staged dot blot solid-phase EIA on nitrocellulose membranes was employed with anti-ABH monoclonal antibodies obtained in immunization of mice with human red cells. 4-chloro-1-naphthol substrate solution was used to visualize the peroxidase label. The results of analysis of salivary and spermatic samples obtained from donors of various groups evidence that this EIA variant may be useful in forensic medicine.
Fine epitope specificity of three anti-A monoclonal antibodies (MA) 1H410, 3F9, and 44F9 was studied by: 1) direct MA binding to synthetic oligosaccharides (OS) linked to polyacrylamide matrix, and 2) inhibition of MA binding to natural antigen by synthetic OS and their polyacrylamide conjugates. It has been established that the antigen binding site of MA 1H10 is specific for tetrasaccharide A (type 3), whereas MAs 3F9 and 44F9 recognize trisaccharide A, the contribution of alpha-L-fucosyl residue being insignificant in the case of 44F9 binding. The correlation of the MAs epitope specificity with their ability to agglutinate red blood cells of A1 and weak A subgroups is discussed.
Fine epitope specificity of ten monoclonal antibodies (MA) agglutinating red blood cells B was studied. Three methods were used: 1) inhibition of MA binding to natural antigen by synthetic oligosaccharides (OS) and their polyacrylamide conjugates, 2) direct MA binding to a series of synthetic OS-polyacrylamide conjugates differing in carbohydrate epitope density, 3) direct MA binding to the affinity sorbents. It is shown that all antibodies studied prefer trisaccharide B determinant Gal-alpha-1-3(Fuc-alpha-1-2) Gal independently of their ability to discriminate serological subgroups of B erythrocytes (B, B(weak), B3). The correlation of the MAs epitope specificity with their ability to agglutinate red blood cells B subgroups is discussed. Of an interest is that MAs which are able to agglutinate any B subgroups also bing the synthetic tetrasaccharide Gal-alpha-1-3(Fuc-alpha-1-2)Gal-beta-1-3GalNAc, a B type 3 determinant.