<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">pmedpharm</journal-id><journal-title-group><journal-title xml:lang="ru">Фармация и фармакология</journal-title><trans-title-group xml:lang="en"><trans-title>Pharmacy &amp; Pharmacology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2307-9266</issn><issn pub-type="epub">2413-2241</issn><publisher><publisher-name>Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.19163/2307-9266-2018-6-4-351-366</article-id><article-id custom-type="elpub" pub-id-type="custom">pmedpharm-314</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ФАРМАЦЕВТИЧЕСКАЯ И ТОКСИКОЛОГИЧЕСКАЯ ХИМИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PHARMACEUTICAL AND TOXICOLOGICAL CHEMISTRY</subject></subj-group></article-categories><title-group><article-title>ФИЗИКО-ХИМИЧЕСКИЕ ИССЛЕДОВАНИЯ ПЧЕЛИНОГО ЯДА  И ПРОДУКТОВ НА ЕГО ОСНОВЕ</article-title><trans-title-group xml:lang="en"><trans-title>PHYSICO-CHEMICAL STUDIES OF APITOXIN AND PRODUCTS  ON ITS BASIS</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бутенко</surname><given-names>Л. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Butenko</surname><given-names>L. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Бутенко Людмила Ивановна – кандидат химических наук, преподаватель кафедры органической химии.</p><p>357500, Пятигорск, пр. Калинина, 11</p></bio><bio xml:lang="en"><p>Butenko Lyudmila Ivanovna – PhD (Chemistry), Lecturer of the Department of Organic Chemistry.</p><p>11, Kalinin ave., Pyatigorsk, 357532</p></bio><email xlink:type="simple">polechka2802@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кулешова</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kuleshova</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кулешова Светлана Анатольевна – кандидат фармацевтических наук, доцент, кафедра фармакологии с курсом клинической фармакологии.</p><p>357500, Пятигорск, пр. Калинина, 11</p></bio><bio xml:lang="en"><p>Kuleshova Svetlana Anatolevna – PhD (Pharmacy), docent of the Department of Pharmacology with the course of Clinical Pharmacology.</p><p>11, Kalinin ave., Pyatigorsk, 357532</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Подгорная</surname><given-names>Ж. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Podgornaya</surname><given-names>J. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Подгорная Жанна Валериевна – кандидат фармацевтических наук.</p><p>Москва, ул. Краснобогатырская, д. 89</p></bio><bio xml:lang="en"><p>Podgornaya Janna Valerievna – PhD (Pharmacy).</p><p>89, Krasnobogatyrskaya Str., 107076</p></bio><email xlink:type="simple">podgornaya_janna@mail.ru</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мыкоц</surname><given-names>Л. П.</given-names></name><name name-style="western" xml:lang="en"><surname>Myikots</surname><given-names>L. P.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мыкоц Лилия Петровна – кандидат фармацевтических наук, доцент, кафедра общей, неорганической и физической химии.</p><p>357500, Пятигорск, пр. Калинина, 11</p></bio><bio xml:lang="en"><p>Myikots Liliya Petrovna – PhD (Pharmacy), docent of the Department of general, inorganic and physical chemistry.</p><p>11, Kalinin ave., Pyatigorsk, 357532</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дмитриев</surname><given-names>А. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Dmitriev</surname><given-names>A. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Дмитриев Александр Борисович – кандидат химических наук, доцент, кафедра аналитической химии.</p><p>357500, Пятигорск, пр. Калинина, 11</p></bio><bio xml:lang="en"><p>Dmitriev Aleksandr Borisovich – PhD (Chemistry), docent of the Department of Analytical Chemistry.</p><p>11, Kalinin ave., Pyatigorsk, 357532</p></bio><email xlink:type="simple">abdmitr2006@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Пятигорский медико-фармацевтический институт – филиал ФГБОУ ВО ВолгГМУ Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Представительство BRACCO Group в России, Региональный директор</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Representative establishment of BRACCO Group in Russia, Regional Director</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>13</day><month>09</month><year>2018</year></pub-date><volume>6</volume><issue>4</issue><fpage>351</fpage><lpage>366</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Бутенко Л.И., Кулешова С.А., Подгорная Ж.В., Мыкоц Л.П., Дмитриев А.Б., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Бутенко Л.И., Кулешова С.А., Подгорная Ж.В., Мыкоц Л.П., Дмитриев А.Б.</copyright-holder><copyright-holder xml:lang="en">Butenko L.I., Kuleshova S.A., Podgornaya J.V., Myikots L.P., Dmitriev A.B.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.pharmpharm.ru/jour/article/view/314">https://www.pharmpharm.ru/jour/article/view/314</self-uri><abstract><p>В настоящее время является актуальным разработка метода количественного определения мелиттина не только в образцах пчелиного яда, но и в продуктах его переработки.</p><p>Целью нашего исследования является изучение физико-химических характеристик основного компонента пчелиного яда – мелиттина. А также разработка методики количественного определения мелиттина в образцах пчелиного яда и в фармацевтических продуктах, полученных на основе пчелиного яда: крем «Софья с пчелиным ядом» и препарат «Апизартрон».</p><sec><title>Материалы и методы</title><p>Материалы и методы. Объектами исследований являлись пчелиный яд и мелиттин, а также образцы мази «Апизартрон» и крема «Софья с пчелиным ядом®», соответствующие требованиям нормативной документации, серийно выпускаемые отечественными и зарубежными производителями. УФ-спектр мелиттина и пчелиного яда регистрировали на спектрофотометре СФ 103 в кварцевых кюветах толщиной 1 см. ИК-спектры исследовали на приборе ИК-Фурье – спектрофотометр ФСМ-1201 ООО «Инфраспек». Определение чистоты мелиттина проводили методом хроматографии.</p></sec><sec><title>Результаты и обсуждение</title><p>Результаты и обсуждение. Для мелиттина, как референтного образца и основного компонента пчелиного яда, были установлены основные физико-химические характеристики. Установлена Tпл. = 190ºС. В УФ-спектре наблюдаются максимумы поглощения, соответствующие 2 пикам: λ max = 225±2 нм и 285±2 нм. В качестве аналитической длины волны необходимо выбрать пик λ=285 нм, так как пик с λ=225 нм связан с поглощением света внутренним (экранированным) бензольным кольцом молекулы триптофана. Характер кривой и положение максимумов спектров мелиттина и раствора яда совпадают, что позволяет использовать мелиттин в качестве стандарта для спектрометрического количественного определения действующих веществ в пчелином яде и препаратах на основе пчелиного яда.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Introduction</title><p>Introduction. Nowadays, it is vitally important to develop a method for quantifying melittin not only in apitoxin samples, but also in the products of its processing.</p><p>The aim of our study is to investigate physical and chemical characteristics of melittin, the main component of apitoxin, as well as the development of methods for the quantitative determination of melittin in the samples of apitoxin and in the pharmaceutical products derived from apitoxin: “Sophia with apitoxin” cream and “Apizartron” ointment.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. The objects of the research were apitoxin and melittin, as well as the samples of “Sophia with apitoxin” cream and “Apizartron” ointment satisfying the requirements of regulatory documentation, produced in lots by domestic and foreign manufacturers. The UV spectra of melittin and apitoxin were registered on SF 103 spectrophotometer in quartz cuvettes with 1 cm thickness. The IR spectra were investigated on the IR-instrument of Fourier – FSM-1201 spectrophotometer, LLC “Infraspek”. The determination of melittin purity was carried out by chromatography.</p></sec><sec><title>Results and discussion</title><p>Results and discussion. The basic physical and chemical characteristics were established for melittin as a reference sample and the main component of apitoxin. The melting temperature was: (Tmelt.)=190ºС. In the UV-spectrum there could be watched the absorption maxima corresponding to 2 peaks: λ max = 225±2 nm and 285±2 nm were observed. As an analytical wavelength, it is necessary to choose the peak λ =285 nm, since the peak with λ =225 nm is associated with the absorption of light by the internal (shielded) benzene ring of the tryptophan molecule. The nature of the curve and the position of the maxima of the spectra of melittin and the apitoxin solution coincide, which makes it possible to use melittin as a standard for spectrometric quantitative determination of the active substances in apitoxin and preparations based on apitoxin.</p></sec><sec><title>Conclusion</title><p>Conclusion. The worked out spectrophotometric methods for the quantitative determination of melittin in apitoxin has been validated by the indices of specificity, accuracy, detection limit, quantitative determination limit, linearity.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>пчелиный яд</kwd><kwd>мелиттин</kwd><kwd>стандартизация</kwd><kwd>спектрофотометрическое определение</kwd><kwd>УФ- и ИК-спектры мелиттина</kwd><kwd>лекарственные препараты на основе пчелиного яда</kwd></kwd-group><kwd-group xml:lang="en"><kwd>apitoxin</kwd><kwd>melittin</kwd><kwd>standardization</kwd><kwd>spectrophotometric determination</kwd><kwd>UV and IR spectra of melittin</kwd><kwd>drugs based on apitoxin</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Bradshaw J.P., Dempsey C.E., Watts A. A combined X-ray and neutron diffraction study of selectively deuterated melittin in phospholipid bilayers: effect of pH // Mol Membr Biol. 1994. Vol. 11. Is. 2. P. 79–86.</mixed-citation><mixed-citation xml:lang="en">Bradshaw JP, Dempsey CE, Watts A. A combined X-ray and neutron diffraction study of selectively deuterated melittin in phospholipid bilayers: effect of pH. Mol Membr Biol. 1994 Apr- Jun;11(2):79–86.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Walsh E.G., Maher S., Devocelle M., O’Brien P.J., Baird A.W., Brayden D.J. High content analysis to determine cytotoxicity of the antimicrobial peptide, melittin and selected structural analogs. Peptides. 2011. Vol. 32. Is. 8. P. 1764–1773. DOI: 10.1016/j.peptides.2011.06.006</mixed-citation><mixed-citation xml:lang="en">Walsh EG, Maher S, Devocelle M, O`Brien PJ, Baird AW, Brayden DJ. High content analysis to determine cytotoxicity of the antimicrobial peptide, melittin and selected structural analogs. Peptides. 2011 Aug;32(8):1764–73. doi:10.1016/j.peptides.2011.06.006</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou J., Zhao J., Zhang S., Shen J., Qi Y., Xue X., Li Y., Wu L., Zhang J., Chen F., Chen L. Quantification of melittin and apamin in bee venom lyophilized powder from Apis mellifera by liquid chromatography-diode array detector-tandem mass spectrometry // Anal Biochem. 2010. Vol. 404. Is. 2. P. 171–178. DOI: 10.1016/j. ab.2010.05.014</mixed-citation><mixed-citation xml:lang="en">Zhou J, Zhao J, Zhang S, Shen J, Qi Y, Xue X, Li Y, Wu L, Zhang J, Chen F, Chen L. Quantification of melittin and apamin in apitoxin lyophilized powder from Apis mellifera by liquid chromatography-diode array detector-tandem mass spectrometry. Anal Biochem. 2010 Sep 15;404(2):171–8. DOI: 10.1016/j.ab.2010.05.014</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Lee W.R., Kim K.H., An H.J., Kim J.Y., Han S.M., Lee K.G., Park K.K. Protective effect of melittin against inflammation and apoptosis on Propionibacterium acnes-induced human THP-1 monocytic cell // Eur J Pharmacol. 2014. Vol. 740. P. 218–226. DOI: 10.1016/j.ejphar.2014.06.058</mixed-citation><mixed-citation xml:lang="en">Lee WR, Kim KH, An HJ, Kim JY, Han SM, Lee KG, Park KK. Protective effect of melittin against inflammation and apoptosis on Propionibacterium acnes-induced human THP-1 monocytic cell. Eur J Pharmacol. 2014 Oct 5;740:218–26. DOI: 10.1016/j.ejphar.2014.06.058</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Stankowski S., Pawlak M., Kaisheva E., Robert C.H., Schwarz G. A combined study of aggregation, membrane affinity and pore activity of natural and modifiedmelittin. Biochim Biophys Acta. 1991. Vol. 1069. P. 77–86.</mixed-citation><mixed-citation xml:lang="en">Stankowski S, Pawlak M, Kaisheva E, Robert CH, Schwarz G. A combined study of aggregation, membrane affinity and pore activity of natural and modifiedmelittin. Biochim Biophys Acta. 1991 Oct 14; 1069(1):77–86.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Choe J.Y., Kim S.K. Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages // Int J Mol Med. 2017 Feb 3. DOI: 10.3892/ijmm.2017.2876</mixed-citation><mixed-citation xml:lang="en">Choe JY, Kim SK. Melittin inhibits osteoclast formation through the downregulation of the RANKL-RANK signaling pathway and the inhibition of interleukin-1β in murine macrophages. Int J Mol Med. 2017 Feb 3. DOI: 10.3892/ijmm.2017.2876</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Gajski G., Garaj-Vrhovac V. Melittin: a lytic peptide with anticancer properties // Environ Toxicol Pharmacol. 2013. Vol. 36. Vol. 2. P. 697–705. DOI: 10.1016/j.etap.2013.06.009</mixed-citation><mixed-citation xml:lang="en">Gajski G, Garaj-Vrhovac V. Melittin: a lytic peptide with anticancer properties. Environ Toxicol Pharmacol. 2013 Sep;36(2):697–705. DOI: 10.1016/j.etap.2013.06.009</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Nordvall S.L., Uhlin T., Einarsson R., Johansson S.G., Ohman S. Bee keepers’ IgG and IgE antibody responses to bee venom studied by means of crossed radioimmunoelectrophoresi // Clin Allergy. 1984. Vol. 14. Is. 4. P. 341–350.</mixed-citation><mixed-citation xml:lang="en">Nordvall SL, Uhlin T, Einarsson R, Johansson SG, Ohman S. Bee keepers` IgG and IgE antibody responses to apitoxin studied by means of crossed radioimmunoelectrophoresi. Clin Allergy. 1984 Jul;14(4):341–50. 9.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Kulkarni H.M., Nagaraj R., Jagannadham M.V. Protective role of E. coli outer membrane vesicles against antibiotics // Microbiol Res. 2015. Vol. 181. P. 1–7. DOI:10.1016/j.micres.2015.07.008</mixed-citation><mixed-citation xml:lang="en">Kulkarni HM, Nagaraj R, Jagannadham MV. Protective role of E. coli outer membrane vesicles against antibiotics. Microbiol Res. 2015 Dec;181:1–7. DOI:10.1016/j.micres.2015.07.008</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Gajski G., Garaj-Vrhovac V. Melittin: a lytic peptide with anticancer properties // Environ Toxicol Pharmacol. 2013. Vol. 36. Is. 2. P. 697–705. DOI: 10.1016/j.etap.2013.06.009</mixed-citation><mixed-citation xml:lang="en">Gajski G, Garaj-Vrhovac V. Melittin: a lytic peptide with anticancer properties. Environ Toxicol Pharmacol. 2013 Sep;36(2):697–705. DOI: 10.1016/j.etap.2013.06.009</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Dempsey C.E. The actions of melittin on membranes // Biochim Biophys Acta. 1990. Vol. 1031. Is. 2. P. 143–161.</mixed-citation><mixed-citation xml:lang="en">Dempsey CE. The actions of melittin on membranes. Biochim Biophys Acta. 1990 May 7;1031(2):143–61.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Choi J.H., Jang A.Y., Lin S., Lim S., Kim D., Park K., Han S.M., Yeo J.H., Seo H.S. Melittin, a honeybee venomderived antimicrobial peptide, may target methicillinresistant Staphylococcus aureus // Mol Med Rep. 2015. Vol. 12. Is. 5. P. 6483–6490. DOI: 10.3892/mmr.2015.4275</mixed-citation><mixed-citation xml:lang="en">Choi JH, Jang AY, Lin S, Lim S, Kim D, Park K, Han SM, Yeo JH, Seo HS. Melittin, a honeyapitoxin derived antimicrobial peptide, may target methicillin resistant Staphylococcus aureus. Mol Med Rep. 2015 Nov;12(5):6483– 90. DOI: 10.3892/mmr.2015.4275</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Demchenko A.P., Kostrzhevskaia E.G. Melittin: structure, properties, interaction with a membrane // Ukr Biokhim Zh (1978). 1986. Vol. 58. Is. 5. P. 92–103.</mixed-citation><mixed-citation xml:lang="en">Demchenko AP, Kostrzhevskaia EG. Melittin: structure, properties, interaction with a membrane. Ukr Biokhim Zh (1978). 1986 Sep-Oct;58(5):92–103. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Ridgway Z., Picciano A.L., Gosavi P.M., Moroz Y.S., Angevine C.E., Chavis A.E., Reiner J.E., Korendovych I.V., Caputo G.A. Functional characterization of a melittin analog containing a non-natural tryptophan analog // Biopolymers. 2015. Vol. 104. Is. 4. P. 384-394. DOI: 10.1002/bip.22624</mixed-citation><mixed-citation xml:lang="en">Ridgway Z, Picciano AL, Gosavi PM, Moroz YS, Angevine CE, Chavis AE, Reiner JE, Korendovych IV, Caputo GA. Functional characterization of a melittin analog containing a non-natural tryptophan analog. Biopolymers. 2015 Jul;104(4):384–394. DOI: 10.1002/bip.22624</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Casado M.P., Macken A., Byrne H.J. Ecotoxicological assessment of silica and polystyrene nanoparticles assessed by a multitrophic test battery // Environ Int. 2013. Vol. 51. P. 97–105. DOI: 10.1016/j.envint.2012.11.001</mixed-citation><mixed-citation xml:lang="en">Casado MP, Macken A, Byrne HJ. Ecotoxicological assessment of silica and polystyrene nanoparticles assessed by a multitrophic test battery. Environ Int. 2013 Jan;51:97–105. DOI: 10.1016/j.envint.2012.11.001</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Tusiimire J., Wallace J., Dufton M., Parkinson J., Clements C.J., Young L., Park J.K., Jeon J.W., Watson D.G. An LCMS method for the assay of melittin in cosmetic formulations containing bee venom // Anal Bioanal Chem. 2015. Vol. 407. Is. 13. P. 3627–3635. DOI: 10.1007/s00216-015-8578-5</mixed-citation><mixed-citation xml:lang="en">Tusiimire J, Wallace J, Dufton M, Parkinson J, Clements CJ, Young L, Park JK, Jeon JW, Watson DG. An LCMS method for the assay of melittin in cosmetic formulations containing apitoxin. Anal Bioanal Chem. 2015 May;407(13):3627–35. DOI: 10.1007/s00216-015-8578-5</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Kokot Z.J., Matysiak J., Urbaniak B., Dereziński P. New CZE-DAD method for honeybee venom analysis and standardization of the product // Anal Bioanal Chem. 2011. Vol. 399. Is. 7. P. 2487–2494. DOI: 10.1007/s00216010-4627-2</mixed-citation><mixed-citation xml:lang="en">Kokot ZJ, Matysiak J, Urbaniak B, Dereziński P. New CZE-DAD method for honeyapitoxin analysis and standardization of the product. Anal Bioanal Chem. 2011 Mar;399(7):2487–94. DOI: 10.1007/s00216-010-4627-2</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Tusiimire J., Wallace J., Dufton M., Parkinson J., Clements C.J., Young L., Park J.K., Jeon J.W., Watson D.G. An LCMS method for the assay of melittin in cosmetic formulations containing bee venom // Anal Bioanal Chem. 2015. Vol. 407. Is. 13. P. 3627–3635. DOI: 10.1007/s00216-015-8578-5</mixed-citation><mixed-citation xml:lang="en">Tusiimire J, Wallace J, Dufton M, Parkinson J, Clements CJ, Young L, Park JK, Jeon JW, Watson DG. An LCMS method for the assay of melittin in cosmetic formulations containing apitoxin. Anal Bioanal Chem. 2015 May;407(13):3627–35. DOI: 10.1007/s00216-015-8578-5</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Zenon J.K., Jan M. Simultaneous determination of major constituents of honeybee venom by LC-DAD // Chromatographia. 2009. Vol. 69. P. 1401–1405.</mixed-citation><mixed-citation xml:lang="en">Zenon JK, Jan M. Simultaneous determination of major constituents of honeyapitoxin by LC-DAD. Chromatographia. 2009;69:1401–5.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Szokan G., Horvath J., Almas M. Liquid chromatographic analysis and separation of polypeptide components from honey bee venoms // J. Liq. Chromatogr. Rel. Technol. 1994. Vol. 17. P. 3333–3349.</mixed-citation><mixed-citation xml:lang="en">Szokan G, Horvath J, Almas M. Liquid chromatographic analysis and separation of polypeptide components from honey apitoxins. J. Liq. Chromatogr. Rel. Technol. 1994;17:3333–49.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Zhao J. Determination of melittin in bee venom by HPLC // Chin. Mod. Instrum. 1998. Vol. 6. P. 44–45.</mixed-citation><mixed-citation xml:lang="en">Zhao J. Determination of melittin in apitoxin by HPLC. Chin. Mod. Instrum. 1998;6:44–5.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Ziyavitdinov Z.F., Inogamov U.K., Sagdiev N.Z., Salikhov S.I. Development of a method for the complex isolation of physiologically active components from bee venom // Chem. Nat. Compounds. 1995. Vol. 31. P. 726–730.</mixed-citation><mixed-citation xml:lang="en">Ziyavitdinov ZF, Inogamov UK, Sagdiev NZ, Salikhov SI. Development of a method for the complex isolation of physiologically active components from apitoxin. Chem. Nat. Compounds. 1995;31:726–30.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou J., Zhao J., Zhang S. Quantification of melittin and apamin in bee venom lyophilized powder from Apis melli- fera by liquid chromatography – diode array detector – tandem mass spectrometry // Anal. Biochem. 2010. Vol. 404. P. 171–178.</mixed-citation><mixed-citation xml:lang="en">Zhou J, Zhao J, Zhang S. Quantification of melittin and apamin in apitoxin lyophilized powder from Apis melli- fera by liquid chromatography – diode array detector – tandem mass spectrometry. Anal. Biochem. 2010;404:171–8.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Demchenko A.P., Kostrzhevskaia E.G. Melittin: structure, properties, interaction with a membrane // Ukr Biokhim Zh (1978). 1986. Vol. 58. Is. 5. P. 92–103.</mixed-citation><mixed-citation xml:lang="en">Demchenko AP, Kostrzhevskaia EG. Melittin: structure, properties, interaction with a membrane. Ukr Biokhim Zh (1978). 1986 Sep-Oct;58(5):92–103. Review. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Омаров Ш.М., Атаев М.Г., Магомедова З.Ш., Омарова З.М. «Роль пчелиного яда и прополиса» // Вестник международной академии наук (русская секция). 2006. Т. 1. С 36–42.</mixed-citation><mixed-citation xml:lang="en">Omarov ShM, Ataev MG, Magomedova ZSh, Omarova ZM. «Rol pchelinogo yada i propolisa» [“The role of bee venom and propolis”]. Vestnik mejdunarodnoy akademii nauk (russkaya sektsiya). 2006;1:36–42. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">ГОСТ 30426-97. Яд-сырец пчелиный. Технические условия. Минск: Межгосударственный совет по стандартизации, метрологии и сертификации, 2000.</mixed-citation><mixed-citation xml:lang="en">GOST 30426-97. YAd-syirets pchelinyiy. Tehnicheskie usloviya [Beef raw bee poison. Technical conditions.]. Minsk: Mejgosudarstvennyiy sovet po standartizatsii, metrologii i sertifikatsii; 2000. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Быков В.А., Демина Н.Б., Кеменова В.А. Изучение влияния различных факторов на высвобождение лекарственных веществ из матричных таблеток // Хим.-фарм. журнал. 2005. №5. С. 40–45.</mixed-citation><mixed-citation xml:lang="en">Byikov VA, Demina NB, Kemenova VA. Izuchenie vliyaniya razlichnyih faktorov na vyisvobojdenie lekarstvennyih veschestv iz matrichnyih tabletok [The study of the influence of various factors on the release of drugs from matrix tablets]. Khimiko-Farmatsevticheskii Zhurnal. 2005;5:40–5. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Хомутов А.Е., Гиноян Р.В., Лушникова О.В., Пурсанов К.А. Апитерапия. Монография. Нижний Новгород: Изд-во ННГУ. 2014. 442 с.</mixed-citation><mixed-citation xml:lang="en">Homutov AE, Ginoyan RV, Lushnikova OV, Pursanov KA. Apiterapiya [Apitherapy]. Monografiya. Nijniy Novgorod: Izd-vo NNGU;2014. 442 p. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Ахмерова Д.И., Ставрианиди А.Н., Родин И.А., Шпигун О.А. Применение метода высокоэффективной жидкостной хроматографии-тандемной масс-спектрометрии для обнаружения характеристичного пептида пчелиного яда – мелиттина. «Заводская лаборатория. Диагностика материалов» № 12. 2014. Том 80. С. 9–15.</mixed-citation><mixed-citation xml:lang="en">Ahmerova DI, Stavrianidi AN, Rodin IA, Shpigun OA. Primenenie metoda vyisokoeffektivnoy jidkostnoy hromatografii-tandemnoy mass-spektrometrii dlya obnarujeniya harakteristichnogo peptida pchelinogo yada – melittina [The use of high-performance liquid chromatography-tandem mass spectrometry for the detection of characteristic peptides of bee venom-melittin]. «Zavodskaya laboratoriya. Diagnostika materialov» N 12. 2014;80:9–15. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Якубке Х.-Д., Ешкайт X.Я. Аминокислоты, пептиды, белки: Пер. с нем. М.: Мир, 1985. 456 c.</mixed-citation><mixed-citation xml:lang="en">Yakubke HD, Eshkayt XYa. Aminokislotyi, peptidyi, belki [Amino acids, peptides, proteins]. Per. s nem. Mockva: Mir; 1985. 456 p. Russian.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Фармакопейная статья «Яд пчелиный» ФС-42-2683-89 (утратила силу с 25 апреля 2001 года). URL: http://docs.cntd.ru/document/902314733 (дата обращения: 14.02.2017)</mixed-citation><mixed-citation xml:lang="en">Farmakopeynaya statya «YAd pchelinyiy» FS-42-2683-89 (utratila silu s 25 aprelya 2001 goda). [Internet]. [cited 2017 Feb 14]. Available from: http://docs.cntd.ru/document/902314733 Russian.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Государственная Фармакопея, XIII издание. ОФС.1.1.0012.15 Валидация аналитических методик. URL: http://pharmacopoeia.ru/ofs-1-1-0012-15-validatsiya-analiticheskih-metodik/ (дата обращения: 14.02.2017)</mixed-citation><mixed-citation xml:lang="en">Gosudarstvennaya Farmacopeia [State Pharmacopoeia]. XIII edition. OFS.1.1.0012.15 Validatsiya analiticheskih metodik. [Internet]. [cited 2017 Feb 14]. Available from: http://pharmacopoeia.ru/ofs-1-1-0012-15-validatsiya-analiticheskih-metodik/ Russian.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
