Human saliva is increasingly being used and validated as a biofluid for diagnosing, monitoring systemic disease status, and predicting disease progression. The discovery of biomarkers in saliva biofluid offers unique opportunities to bypass the invasive procedure of blood sampling by using oral fluids to evaluate the health condition of a patient. Saliva biofluid is clinically relevant since its components can be found in plasma. As salivary lipids are among the most essential cellular components of human saliva, there is great potential for their use as biomarkers. Lipid composition in cells and tissues change in response to physiological changes and normal tissues have a different lipid composition than tissues affected by diseases. Lipid imbalance is closely associated with a number of human lifestyle-related diseases, such as atherosclerosis, diabetes, metabolic syndromes, systemic cancers, neurodegenerative diseases, and infectious diseases. Thus, identification of lipidomic biomarkers or key lipids in different diseases can be used to diagnose diseases and disease state and evaluate response to treatments. However, further research is needed to determine if saliva can be used as a surrogate to serum lipid profiles, given that highly sensitive methods with low limits of detection are needed to discover salivary biomarkers in order to develop reliable diagnostic and disease monitoring salivary tests. Lipidomic methods have greatly advanced in recent years with a constant advance in mass spectrometry (MS) and development of MS detectors with high accuracy and high resolution that are able to determine the elemental composition of many lipids.

In this article, we demonstrate how an original effective “metal-free” and “chromatography-free” route for the synthesis of 3-thiocyanatopyrazolo[1,5-a]pyrimidines has been developed. It is based on electrooxidative (anodic) C–H thiocyanation of 5-aminopyrazoles by thiocyanate ion leading to 4-thiocyanato-5-aminopyrazoles (stage 1, yields up to 87%) following by their chemical condensation with 1,3-dicarbonyl compounds or their derivatives (stage 2, yields up to 96%). This method is equally effective for the synthesis of 3-thiocyanatopyrazolo[1,5-a]pyrimidines, both without substituents and with various donor (acceptor) substituents in the pyrimidine ring.

Introduction. One of the purposes of dissolution profile comparison is to establish the equivalence of dissolution profiles of the studied drug and the comparison drug.Text. According to the current regulatory documents, the main tool for quantitative confirmation of equivalence of drug release profiles is the calculation of the similarity factor (f 2). However, it does not consider the form of dissolution profiles, incomplete release of the drug substance, time correlation, and is not susceptible to the «outliers», which leads to false positive results. Special attention should be paid to the dissolution of drugs with high variability, which is not eliminated by either increasing the sample or changing the sampling scheme. If f 2 is not used, it is necessary to use model-dependent and model-independent methods that are statistically correct, and their use is sufficiently justified (difference factor f 1 , Weibull distribution function, comparison of release degrees at different time points (according to the student's t-criterion). However, these models have an empirical nature that calls into question the application of such methods. Multivariate analysis is widely discussed in the literature and can be used to compare the similarity of dissolution with the assumption that the data has a normal distribution. The most common methods for checking similarity of dissolution profiles for highly variable drugs are the Mahalanobis distance test and the bootstrap for f 2. There is a document of EMA about suitability of the Mahalanobis distance as a tool to assess the comparability of drug dissolution profiles and to a larger extent to emphasise the importance of confidence intervals to quantify the uncertainty around the point estimate of the chosen metric. The bootstrap methodology for f 2 does not provide a clear understanding of the application to dissolution profile comparison for incomplete-release drugs, particularly in biorelevant environments. The «T2EQ» function, based on the Mahalanobis distance for highly variable drugs (Hoffelder), gives undefined results in practice.Conclusion. The topic of equivalence of dissolution profiles requires discussion, since it is shown that the convergence factor is outdated and cannot be adequately applied. The use of modern methods does not have a clear regulatory confirmation by the regulatory authority. In the published scientific literature, several statistical methods have been explored and compared for their design and performance. It is necessary to develop a clear plan (decision treeы) for conducting the procedure for equivalence of dissolution profiles, employing a range of statistical methods.

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Introduction. Recently, there has been a growing trend in the number of obese and overweight patients. To date, sibutramine is the most effective drug for treating obesity and overweight. The drug is an inhibitor of the reuptake of serotonin and norepinephrine, which leads to a decrease in hunger, and therefore, to weight loss.Aim. To develop and validate a methodology for the determination of sibutramine in drugs by capillary electrophoresis (CE) using an ultraviolet diode array detector.Materials and methods. Quantitative determination of sibutramine in drugs was carried out using the CE method with an ultraviolet diode array detector. A solution of phosphate buffer 50 mmol pH = 7.0 was used as a solvent and working electrolyte; to separate the peaks – quartz capillary 56 cm, 50 μm.Results and discussion. The developed method was validated according to the following parameters: specificity, linearity, correctness, precision, limit of detection and limit of quantification.Conclusion. A method for the quantitative determination of sibutramine in drugs by the CE method using an ultraviolet diode array detector has been developed and validated. This method meets all the requirements of General Pharmacopoeia Monograph 1.1.0012.15 «Validation of the analytical method» and can be used to control the quality of drugs, the active pharmaceutical substance of which is sibutramine.