Pharmaceutical Chemistry Journal (v.48, #5)

Current Criteria for Studies of Drug Bioequivalence: Harmonization of National Standards by A. S. Smirnov; A. Schneider; M. Yu. Frolov; V. I. Petrov (303-309).
Harmonization of national standards for drugs is one of the most relevant contemporary tasks for states, and the importance of this task for Russia increased with entry into the World Trade Organization (WTO). Apart from laws regulating medicines, a large body of subordinate legislation also requires review and updating. The guidelines for studies of drug bioequivalence are among the definitive normative documents for drug registration and quality control. The expert and medical communities are of the view that the current Russian guidelines do not meet international requirements and require revision. Some of the international criteria used in studies of drug bioequivalence are presented here. With the aim of increasing the quality of medicines on the Russian pharmaceutical market, we discuss current and proposed additional indicators for studies of bioequivalence for amendments and additions to allow documents to reach international standards.
Keywords: bioequivalence; harmonization of national standards

Partition coefficients of polyuronides and their salts (pectin, sodium alginate, calcium alginate) in a water/octan-1-ol system were measured at different temperatures and different pH values. Changes in the thermodynamic functions accompanying interphase partition (enthalpy, entropy, Gibbs free energy) were identified to evaluate the potential for distribution to occur spontaneously.
Keywords: polyuronides; distribution in biological substrates

Synthesis and Anti-Inflammatory Activity of Ibuprofen Esters by I. A. Kravchenko; M. V. Kireva; E. A. Alekseeva (313-316).
The anti-inflammatory activities of new ibuprofen esters with alcohol residues of different lengths were studied. These compounds were found to have anti-inflammatory and antiedema activities comparable to and in some cases greater than those of equimolar quantities of ibuprofen.
Keywords: NSAID; carrageenan; anti-inflammatory activity; ibuprofen esters; intragastric administration

Structural Analysis of Leukotriene B4 (LBT4) Receptor (BLT1 AND BLT2) Antagonists by V. R. Khairullina; I. A. Taipov; A. Ya. Gerchikov; M. N. Vasil’ev; F. S. Zarudii; H. Boegel (317-322).
The structural characteristics typical of highly and moderately effective antagonists of BLT1 and BLT2 receptors were identified and the extents of their influences on the target property were evaluated. Two models for predicting inhibitory activity were constructed for series of sulfur-, nitrogen- and oxygen-containing heterocyclic compounds with significant prognostic levels of greater than 80% using two methods based on sample recognition theory. These structural patterns can be used for virtual screening of potential drugs for antiallergic activity associated with blockade of leukotriene LTB4-sensitive BLT1 and BLT2 receptors.
Keywords: Structure-properties relationships; leukotriene LTB4 ; BLT1 and BLT2 receptors; structural descriptors

Chemical Studies of Eucalyptus Tincture by E. N. Zhukovich; L. M. Bobrenko; M. Yu. Semenova; S. Yu. Bokareva (323-327).
The chemical composition of eucalyptus tincture was studied by extracting and identifying terpenoids – α-terpineol, β-eudesmol, cryptomeridiol, and C-methylflavones – eucalyptin and 6,8-dimethyl-5,7-dihydroxy-4′-methoxyflavone. Methods for assay of C-methylflavones and flavonoids were developed on the basis of spectrophotometric estimation of colored complexes obtained by treatment with aluminum chloride in acidic conditions. The standard for assay of C-methylflavones was a eucalyptin solution with λmax of 388 nm; the standard for flavonoids was a quercetin solution with λmax of 417 ± 5 nm. The C-methylflavone content was 0.0058% and the mean flavonoid content was 0.04%. These methods can be used as an alternative for standardization of eucalyptus tincture.
Keywords: eucalyptus tincture; chemical analysis; terpenoids; α-terpineol; β-eudesmol; cryptomeridiol; C-methylflavones; eucalyptin; 6,8-dimethyl-5,7-dihydroxy-4′-methoxyflavone; mass spectra; 1H NMR spectrum; flavonoids; standardization

Administration of steroid glycosides of both the spirostanol type, where the active substance is deltonin, and the furostanol type, the main components of which are deltoside and protodioscine, before transplantation of Ehrlich carcinoma (EC) and during its growth had no effect on the body’s resistance to tumor cells, with no effect on the latent period of formation of tumor nodules or the rate of tumor growth. Testing in a therapeutic regimen demonstrated a tendency to stimulation of EC growth in response to spirostanol glycosides. At the same time, treatment with furostanol glycosides showed weak, statistically insignificant, inhibition of tumor growth, in terms of both tumor volume and tumor mass.
Keywords: Allium schoenoprasum L., steroid glycosides; transplanted tumors, mice

Biologically Active Substances from European Guelder Berry Fruits by I. B. Perova; A. A. Zhogova; A. V. Cherkashin; K. I. Éller; G. V. Ramenskaya; I. A. Samylina (332-339).
Fresh-frozen European guelder berry (Viburnum opulus L.) fruits collected in the Tambov, Moscow, and Tver Provinces were studied. The total contents and profiles of biologically active substances (BAS) in European guelder berry fruits were studied, including anthocyanins, proanthocyanidins, flavonones, diydroxycinnamic acids, iridoids, organic acids, and carbohydrates; antiradical activity in the in vitro DPPH test was also studied. These data on specific minor BAS can be used for standardization in assessments of the potential activity of drugs and biologically active food additives based on European guelder berry fruits.
Keywords: European guelder berry; Viburnum opulus ; anthocyanins; flavonoids; chlorogenic acid; iridoids; DPPH

Use of an F Complex in the Pilot-Scale Production of Z-Phe-D-Trp-Lys(ε-Boc)OH by A. N. Balaev; V. N. Osipov; V. E. Fedorov (340-342).
A method for using an F complex for pilot-scale production of Z-Phe-D-Trp-Lys(ε-Boc)OH – a protected tripeptide used in making synthetic analogs of somatostatin is described. This method involves regeneration of pentafluorophenol and allows the target compound to be prepared with a main substance content of ~99%.
Keywords: F complex; peptide synthesis; manufacture; synthetic analogs of somatostatin

Kinetics and Mechanism of Synthesis of Novocaine in the Presence of Palladium-Containing Polymers by M. G. Abdullaev; Z. Sh. Abdullaeva; M. V. Klyuev; Z. G. Gebekova (343-346).
The kinetics and mechanism of hydrogenation of p-nitrobenzoic acid ethyl ester and transesterification of the resulting Anestezin (benzocaine) by diethylaminoethanol on palladium-containing polymers were studied. The kinetic data obtained here suggest a mechanism for transesterification in the presence of acid and alkali. Free functional groups of the weakly basic and strongly basic anion resins are shown to be involved in transesterification. An improved method for preparing novocaine in mild conditions (t = 45°C, hydrogen pressure 1 atm.) is proposed; this is more efficient than the industrial process.
Keywords: kinetics; catalysis; mechanism; palladium-containing polymers; novocaine

Hydrolysis of bicaret was found to require stringent conditions – high temperature and a strongly acidic medium. These studies show that injection solutions of bicaret can be acidified.
Keywords: bicaret; hydrolytic stability; hydrolysis products; enterosorbent; hydrolysis constant

Studies of the Physicochemical Properties of a New Compound with Kappa-Opioid Agonist Activity, RU 1205, and Development of an Analytical Method by A. A. Illarionov; L. N. Grushevskaya; L. M. Gaevaya; M. E. Dudenkova; N. I. Avdyunina; B. M. Pyatin; F. S. Baiburtskii; V. P. Lezina (350-356).
The aim of the present work was to study the physicochemical properties of a new compound with kappa-opioid agonist activity, RU 1205, and to develop methods for qualitative and quantitative analysis of RU 1205 substance. Studies were performed using IR, UV, and 1H NMR spectroscopy, high-performance liquid chromatography, gas–liquid chromatography, and acid–base titration in non-aqueous medium.
Keywords: RU 1205; benzimidazole; IR spectroscopy; UV spectroscopy; 1H NMR spectroscopy; high-performance liquid chromatography; HPLC; gas–liquid chromatography; GLC; non-aqueous titration