ÈÌÌÓÍÎÃËÎÁÓËÈÍÛ

Èììóíîãëîáóëèí ÷åëîâåêà íîðìàëüíûé äëÿ âíóòðèâåííîãî ââåäåíèÿ ÿâëÿåòñÿ íàèáîëåå âîñòðå-áîâàííûì â êëèíèêå. Ïîòðåáíîñòè ìèðîâîãî ðûíêà â ýòîì ïðåïàðàòå åùå íå óäîâëåòâîðåíû ïðîèçâîäèòå-ëÿìè ïðåïàðàòîâ êðîâè.

 òðåáîâàíèÿõ ÅÔ ê èììóíîãëîáóëèíàì [10, 11]

îòñóòñòâóþò ïîêàçàòåëè: «Ïðîçðà÷íîñòü», «Öâåò-íîñòü», «Ìåõàíè÷åñêèå âêëþ÷åíèÿ», «Èçâëåêàåìûé îáúåì», «Òåðìîñòàáèëüíîñòü», «Ñòàáèëèçàòîðû»,

«Ôðàêöèîííûé ñîñòàâ», «Àíîìàëüíàÿ òîêñè÷íîñòü»,

«Âèðóñíàÿ áåçîïàñíîñòü». Ðàçëè÷àþòñÿ ïîäõîäû ê îïðåäåëåíèþ ïîêàçàòåëåé «Ïîäëèííîñòü», «Îáùèé áåëîê», «Ïîòåðÿ â ìàññå ïðè âûñóøèâàíèè».  ÃÔ âïåðâûå ââåäåí ïîêàçàòåëü «Áàêòåðèàëüíûå ýíäîòîê-ñèíû» â êà÷åñòâå àëüòåðíàòèâíîãî ðàçäåëó «Ïèðîãåí-íîñòü». Òàêæå â ÷èñëî êîíòðîëèðóåìûõ â ïðåïàðàòàõ èììóíîãëîáóëèíîâ ïàðàìåòðîâ ñîãëàñíî ÅÔ [10, 11]

âõîäÿò ïîêàçàòåëè «Èììóíîãëîáóëèí À» è «Àíòèòåëà ê ïîâåðõíîñòíîìó àíòèãåíó âèðóñà ãåïàòèòà », îò-ñóòñòâóþùèå â îòå÷åñòâåííûõ ÔÑ. Çàïàäíûå òðåáî-âàíèÿ ê ïîñëåäíåìó ïîêàçàòåëþ îñíîâàíû íà âñåîá-ùåé èììóíèçàöèè äîíîðîâ, è íîðìèðîâàíèå êîëè÷å-ñòâà àíòèòåë ïîçâîëÿåò ãàðàíòèðîâàòü ñâÿçûâàíèå îñòàòî÷íîé êîíöåíòðàöèè âèðóñà ïðè åãî ïîïàäàíèè â ïëàçìó. Òðåáîâàíèÿ ê ïîêàçàòåëÿì «Ìîëåêóëÿðíûå ïàðàìåòðû», «Àíòè-À, àíòè- ãåìàããëþòèíèíû»,

«Àíòèêîìïëåìåíòàðíàÿ àêòèâíîñòü», «Îñìîëÿëü-íîñòü», «Àíòè-D àíòèòåëà» â ÃÔ àíàëîãè÷íû òðåáî-âàíèÿì ÅÔ [10, 11]. Òðåáîâàíèÿ ê èììóíîãëîáóëèíó äëÿ âíóòðèâåííîãî ââåäåíèÿ îòå÷åñòâåííîé ÔÑ â îò-ëè÷èå îò ÅÔ äîïóñêàþò ïîÿâëåíèå â ïðîöåññå õðàíå-íèÿ íåçíà÷èòåëüíîãî îñàäêà, à ê èììóíîãëîáóëèíó äëÿ âíóòðèìûøå÷íîãî ââåäåíèÿ ïî ïîêàçàòåëþ

«Îïèñàíèå» íå ðàçðåøåíû ñâåòëî-êîðè÷íåâûå îòòåí-êè ðàñòâîðà ïðåïàðàòà, à ïî ïîêàçàòåëþ «Ýëåêðîôî-ðåòè÷åñêàÿ îäíîðîäíîñòü» äîïóñêàåòñÿ â 2 ðàçà ìåíü-øå ïðèìåñåé.

4. ÔÀÊÒÎÐÛ ÑÂÅÐÒÛÂÀÍÈß ÊÐÎÂÈ

 ÃÔ XIII âïåðâûå ââåäåíû òðåáîâàíèÿ ê ïðåïà-ðàòàì ôàêòîðîâ ñâåðòûâàíèÿ êðîâè VII, VIII, IX è ôàêòîðà Âèëëåáðàíäà. Òðåáîâàíèÿ ê ýòèì ïðåïàðà-òàì â îñíîâíîì ñîîòâåòñòâóþò òðåáîâàíèÿì ÅÔ [12–15], ò.ê. â Ðîññèéñêîé Ôåäåðàöèè íåò èõ ìàññî-âîãî ïðîèçâîäñòâà.

Äëÿ òîãî ÷òîáû ñîçäàòü ÔÑ íà ôàêòîðû ñâåðòûâà-íèÿ, áûëà ðàçðàáîòàíà ÎÔÑ.1.8.2.0003.15 «Îïðåäåëå-íèå àêòèâíîñòè ôàêòîðîâ ñâåðòûâàíèÿ êðîâè» «Îï-ðåäåëåíèå àêòèâíîñòè ôàêòîðîâ ñâåðòûâàíèÿ êðîâè».

 îñíîâå ìåòîäîâ îïðåäåëåíèÿ àêòèâíîñòè ôàêòîðîâ ñâåðòûâàíèÿ ëåæàò îäèíàêîâûå ïðèíöèïû. Ýòî ïî-çâîëèëî îáúåäèíèòü ìåòîäèêè, èñïîëüçóåìûå ïðè îï-ðåäåëåíèè âñåõ ôàêòîðîâ ñâåðòûâàíèÿ, â îäíîé ÎÔÑ, íåñìîòðÿ íà âîçìîæíûå ðàçëè÷èÿ â òåõíèêå ïîñòà-íîâêè ìåòîäà â çàâèñèìîñòè îò èñïîëüçóåìîãî îáîðó-äîâàíèÿ (â ïðîáèðêàõ èëè ïëàíøåòàõ, ñ èñïîëüçîâà-íèåì ñïåêòðîôîòîìåòðîâ, êîàãóëîìåòðîâ èëè ñïå-öèàëèçèðîâàííûõ ðîáîòèçèðîâàííûõ ïðèáîðîâ).

Òàêèì îáðàçîì, îòå÷åñòâåííûå òðåáîâàíèÿ ê ïðå-ïàðàòàì êðîâè â íàñòîÿùåå âðåìÿ åùå îòëè÷àþòñÿ îò åâðîïåéñêèõ. Öåíòðàëüíîé çàäà÷åé ïîñëåäóþùèõ èç-äàíèé ÃÔ äîëæíà áûòü èõ äàëüíåéøàÿ ãàðìîíèçàöèÿ ñ ÅÔ.

Âñå òðåáîâàíèÿ è íîðìû äëÿ ïðåïàðàòîâ êðîâè, âíåñåííûõ â ÃÔ XIII ÔÑ, àïðîáèðîâàíû íà ñåðèéíûõ îáðàçöàõ îòå÷åñòâåííûõ è çàðóáåæíûõ ïðîèçâîäèòå-ëåé ñîòðóäíèêàìè îòäåëà ýêñïåðòèçû ÔÃÁÓ ÃÍÖ ÌÇ ÐÔ: ñòàðøèìè íàó÷íûìè ñîòðóäíèêàìè: êàíä. áèîë.

íàóê Â. Ñ. Èâàíîâîé, êàíä. õèì. íàóê Ñ. Ã. Áåêñàå-âûì, êàíä. õèì. íàóê Å. Â. Ìèõàéëîâîé, íàó÷íûìè ñîòðóäíèêàìè: êàíä. áèîë. íàóê Ï. À. Ôëåãîíòîâûì, Í. Í. Ïàíîâîé, Ë. À. Òåðåíòüåâîé, èíæåíåðàìè:

Ñ. Ñ. Íåõàåâñêîé, Î. Í. ×àðûêîâîé.

ËÈÒÅÐÀÒÓÐÀ

1. Ïëàçìà äëÿ ôðàêöèîíèðîâàíèÿ. ÔÑ 3.3.2.0001.15.

2. Àëüáóìèí ÷åëîâåêà. ÔÑ 3.3.2.0006.15.

3. Èììóíîãëîáóëèí ÷åëîâåêà íîðìàëüíûé. ÔÑ 3.3.2.0007.15.

4. Èììóíîãëîáóëèí ÷åëîâåêà íîðìàëüíûé äëÿ âíóòðèâåííîãî ââåäåíèÿ. ÔÑ 3.3.2.0008.15.

5. Ãîñóäàðñòâåííàÿ ôàðìàêîïåÿ ÑÑÑÐ. 11-å èçä. Âûï. 1, 2. Ì.: Ìå-äèöèíà; 1987, 1990.

6. Ãîñóäàðñòâåííàÿ ôàðìàêîïåÿ Ðîññèéñêîé Ôåäåðàöèè. 12-å èçä. ×àñòü 1. Ì.: ÍÖÝÑÌÏ; 2007.

7. European Pharmacopoeia. 8th edition. Strasbourg: EDQM; 2013.

8. Human Plasma for fractionation. Ìîíîãðàôèÿ ÅÔ8 0853.

9. Human Albumin solution. Ìîíîãðàôèÿ ÅÔ8 0255.

10. Human normal Immunoglobulin. Ìîíîãðàôèÿ ÅÔ8 0338.

11. Human normal Immunoglobulin for intravenous administration. Ìî-íîãðàôèÿ ÅÔ8 0918.

12. Human von Willebrand factor. Ìîíîãðàôèÿ ÅÔ8 2298.

13. Human coagulation factor VII. Ìîíîãðàôèÿ ÅÔ8 1224.

14. Human coagulation factor VIII. Ìîíîãðàôèÿ ÅÔ8 0275.

15. Human coagulation factor IX. Ìîíîãðàôèÿ ÅÔ8 1223.

ÎÁ ÀÂÒÎÐÀÕ

Ôåäåðàëüíîå ãîñóäàðñòâåííîå áþäæåòíîå ó÷ðåæäåíèå «Ãåìàòîëîãè÷åñêèé íàó÷íûé öåíòð» Ìèíèñòåðñòâà çäðàâîîõðàíåíèÿ Ðîññèéñêîé Ôåäåðàöèè. Ðîññèéñêàÿ Ôåäåðàöèÿ, 125167, Ìîñêâà, Íîâûé Çûêîâñêèé ïðîåçä, 4.

Êàðÿêèí Àëåêñàíäð Âàäèìîâè÷. Çàâåäóþùèé ëàáîðàòîðèåé ýêñïåðòèçû ñðåäñòâ òðàíñôóçèîííîé òåðàïèè, ä-ð áèîë. íàóê, ïðîô.

Ñêîöåëÿñ Åëåíà Äìèòðèåâíà.Çàâåäóþùàÿ ëàáîðàòîðèåé êîíòðîëÿ âèðóñíîé áåçîïàñíîñòè ïðåïàðàòîâ è êîìïîíåíòîâ êðîâè, êàíä. áèîë. íàóê.

Ñðàâíåíèå òðåáîâàíèé Ãîñóäàðñòâåííîé ôàðìàêîïåè XIII èçäàíèÿ è Åâðîïåéñêîé ôàðìàêîïåè ê ïðåïàðàòàì èç ïëàçìû êðîâè ÷åëîâåêà

ÑÒÀÍÄÀÐÒÈÇÀÖÈßÈÊÎÍÒÐÎËÜÊÀ×ÅÑÒÂÀËÅÊÀÐÑÒÂÅÍÍÛÕÑÐÅÄÑÒÂ

ÀÄÐÅÑ ÄËß ÏÅÐÅÏÈÑÊÈ

Êàðÿêèí Àëåêñàíäð Âàäèìîâè÷; [email protected]

COMPARISON OF THE STATE PHARMACOPOEIA, XIII EDITION AND THE EUROPEAN PHARMACOPOEIA REQUIREMENTS

FOR HUMAN PLASMA PRODUCTS A. V. Karyakin, E. D. Skotselyas

Federal State Budgetary Institution «Hematology Research Center»

of the Ministry of Health of the Russian Federation, 125167, Moscow, Russia

Abstract:Russian requirements for main products derived from human plasma used to be laid out in several nonintegrated monographs that have been recently included into the State Pharmacopoeia of the Russian Federation, XIII edition. The present article compares requirements for the quality of human plasma products that are contained in the State Pharmacopoeia, XIII edition and in the Euro-pean Pharmacopoeia.

Key words:State Pharmacopoeia; European Pharmacopoeia; pharmacopoeial monographs; human plasma products; plasma for frac-tionation; albumin; immunoglobulins; blood-coagulation factors; methods of blood products quality control.

For citation:Karyakin AV, Skotselyas ED. Comparison of State Pharmacopoeia, XIII edition and the European Pharmacopoeia require-ments for human plasma products. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products 2016; (2): 50–52.

REFERENCES

1. Plasma for fractionation. FS 3.3.2.0001.15 (in Russian).

2. Human albumin. FS 3.3.2.0006.15 (in Russian).

3. Human immunoglobulin normal. FS 3.3.2.0007.15 (in Russian).

4. Human immunoglobulin normal intravenous. FS 3.3.2.0008.15 (in Russian).

5. The State Pharmacopoeia of the USSR. 11th ed. V. 1, 2. Moscow:

Meditsina; 1987, 1990 (in Russian).

6. The State Pharmacopoeia of the Russian Federation. 12th ed. V. 1.

Moscow: NCESMP; 2007 (in Russian).

7. European Pharmacopoeia. 8th edition. Strasbourg: EDQM; 2013.

8. Human Plasma for fractionation. Monograph Ph. Eur.8 0853 (in Russian).

9. Human Albumin solution. Monograph Ph. Eur.8 0255 (in Russian).

10. Human normal Immunoglobulin. Monograph Ph. Eur.8 0338 (in Rus-sian).

11. Human normal Immunoglobulin for intravenous administration. Mo-nograph Ph. Eur.8 0918 (in Russian).

12. Human von Willebrand factor. Monograph Ph. Eur.8 2298 (in Russi-an).

13. Human coagulation factor VII. Monograph Ph. Eur.8 1224 (in Russi-an).

14. Human coagulation factor VIII. Monograph Ph. Eur.8 0275 (in Russi-an).

15. Human coagulation factor IX. Monograph Ph. Eur.8 1223 (in Russian).

AUTHORS

Federal State Budgetary Institution «Hematology Research Center» of the Ministry of Health of the Russian Federation, Noviy Zykovsky passage 4, Moscow 125167, Russian Federation.

Karyakin AV. Head of Laboratory of examination of transfusion therapy. Doctor of Biological Sciences, professor.

Skotselyas ED. Head of Laboratory of viral safety control of drugs and blood components. Candidate of Biological Sciences.

À. Â. Êàðÿêèí, Å. Ä. Ñêîöåëÿñ

ÑÒÀÍÄÀÐÒÈÇÀÖÈßÈÊÎÍÒÐÎËÜÊÀ×ÅÑÒÂÀËÅÊÀÐÑÒÂÅÍÍÛÕÑÐÅÄÑÒÂ

© ÊÎËËÅÊÒÈÂ ÀÂÒÎÐÎÂ, 2016 ÓÄÊ 615.076

Èñïîëüçîâàíèå ìåòîäà ßÌÐ-ñïåêòðîñêîïèè â ôàðìàêîïåéíîì àíàëèçå

Ñ. Â. Ìîèñååâ, Â. È. Êðûëîâ, Í. Å. Êóçüìèíà, Â. À. ßøêèð, Â. À. Ìåðêóëîâ

Ôåäåðàëüíîå ãîñóäàðñòâåííîå áþäæåòíîå ó÷ðåæäåíèå

«Íàó÷íûé öåíòð ýêñïåðòèçû ñðåäñòâ ìåäèöèíñêîãî ïðèìåíåíèÿ»

Ìèíèñòåðñòâà çäðàâîîõðàíåíèÿ Ðîññèéñêîé Ôåäåðàöèè, 127051, Ìîñêâà, Ðîññèÿ

Ñòàòüÿ ïîñòóïèëà 18.01.2016 ã. Ïðèíÿòà ê ïå÷àòè 08.06.2016 ã.

Ðåçþìå:Ïîêàçàíà âîçìîæíîñòü ïðèìåíåíèÿ ìåòîäà ñïåêòðîñêîïèè ìóëüòèÿäåðíîãî ìàãíèòíîãî ðåçîíàíñà äëÿ êîìïëåêñíî-ãî, ýêñïðåññíîãî è íàäåæíîãî îïðåäåëåíèÿ îñíîâíûõ ïîêàçàòåëåé êà÷åñòâà ëåêàðñòâåííûõ ñóáñòàíöèé ïðè ïðîâåäåíèè ôàð-ìàêîïåéíîãî àíàëèçà.

Êëþ÷åâûå ñëîâà:ßÌÐ-ñïåêòðîñêîïèÿ; ôàðìàêîïåéíûé àíàëèç; ñòðóêòóðíàÿ èíòåðïðåòàöèÿ ßÌÐ-ñïåêòðîâ; ïîäëèííîñòü ëåêàðñòâåííûõ ñóáñòàíöèé; êîëè÷åñòâåííîå îïðåäåëåíèå; ìîëåêóëÿðíî-ìàññîâîå ðàñïðåäåëåíèå; ìîëÿðíîå çàìåùåíèå.

Áèáëèîãðàôè÷åñêîå îïèñàíèå:Ìîèñååâ ÑÂ, Êðûëîâ ÂÈ, Êóçüìèíà ÍÅ, ßøêèð ÂÀ, Ìåðêóëîâ ÂÀ. Èñïîëüçîâàíèå ìåòîäà ßÌÐ-ñïåêòðîñêîïèè â ôàðìàêîïåéíîì àíàëèçå. Âåäîìîñòè Íàó÷íîãî öåíòðà ýêñïåðòèçû ñðåäñòâ ìåäèöèíñêîãî ïðèìåíå-íèÿ 2016; (2): 53–57.

Îäíèì èç îñíîâíûõ íàïðàâëåíèé ñîâåðøåíñòâî-âàíèÿ ìåòîäîëîãèè ôàðìàöåâòè÷åñêîé ýêñïåðòèçû ëåêàðñòâåííûõ ñóáñòàíöèé (ËÑ) â íàøåé ñòðàíå ÿâ-ëÿåòñÿ ðàçðàáîòêà è âíåäðåíèå íîâûõ àíàëèòè÷åñêèõ ìåòîäîâ êîíòðîëÿ êà÷åñòâà ËÑ, îñíîâàííûõ íà ñîâðå-ìåííûõ òåõíîëîãèÿõ. Ïðåäïî÷òåíèå îòäàåòñÿ ïðÿ-ìûì íåäåñòðóêòèâíûì ìåòîäàì àíàëèçà, îòâå÷àþ-ùèì òðåáîâàíèÿì èíôîðìàòèâíîñòè, ýêñïðåññíîñòè è äîñòîâåðíîñòè, êîòîðûå ïîçâîëÿþò èññëåäîâàòü õè-ìè÷åñêèå ïðåâðàùåíèÿ è óñòàíàâëèâàòü ñòðóêòóðû ïîáî÷íûõ è ïðîìåæóòî÷íûõ ïðîäóêòîâ íà âñåõ ñòàäè-ÿõ àíàëèòè÷åñêîãî êîíòðîëÿ. Áîëåå äðóãèõ òàêèì òðå-áîâàíèÿì ñîîòâåòñòâóåò ìåòîä ñïåêòðîñêîïèè ÿäåð-íîãî ìàãíèòÿäåð-íîãî ðåçîíàíñà (ßÌÐ). Èñïîëüçîâàíèå ìåòîäà ßÌÐ äëÿ ðåøåíèÿ àíàëèòè÷åñêèõ çàäà÷ íà÷à-ëîñü â íà÷àëå 50-õ ãîäîâ ïðîøëîãî âåêà ñ ðàçðàáîòêîé êîíöåïöèè õèìè÷åñêîãî ñäâèãà è ñïèí-ñïèíîâîãî âçàèìîäåéñòâèÿ.  íàñòîÿùåå âðåìÿ äàííûé ìåòîä îïèñàí â Ãîñóäàðñòâåííîé ôàðìàêîïåå XII èçäàíèÿ (ÃÔ XII) [1] è âåäóùèõ ôàðìàêîïåÿõ ìèðà (Åâðîïåé-ñêîé, ÑØÀ, ßïîíèè [2–4]), ãäå îí ðåêîìåíäîâàí äëÿ óñòàíîâëåíèÿ ïîäëèííîñòè ðÿäà ëåêàðñòâåííûõ ñóá-ñòàíöèé (íàïðèìåð, òîáðàìèöèíà, áóçåðåëèíà, ãîçå-ðåëèíà, íèçêîìîëåêóëÿðíîãî ãåïàðèíà, îðôåíàäðèíà öèòðàòà, ýíîêñàïàðèíà íàòðèÿ è äð.). Äëÿ îïðåäåëå-íèÿ äðóãèõ ïîêàçàòåëåé êà÷åñòâà ËÑ (èäåíòèôèêàöèÿ ïðèìåñåé è îñòàòî÷íûõ îðãàíè÷åñêèõ ðàñòâîðèòåëåé, êîëè÷åñòâåííîå îïðåäåëåíèå, èññëåäîâàíèå ñòàáèëü-íîñòè) ïî-ïðåæíåìó ïðèìåíÿþò òðàäèöèîííûå ôè-çèêî-õèìè÷åñêèå ìåòîäû àíàëèçà, â ïåðâóþ î÷åðåäü ðàçëè÷íûå âàðèàíòû õðîìàòîãðàôèè (ÃÆÕ, ÂÝÆÕ, òîíêîñëîéíàÿ õðîìàòîãðàôèÿ), à òàêæå ÈÊ-ñïåêòðî-ñêîïèþ è ÓÔ-ñïåêòðîôîòîìåòðèþ [1], õàðàêòåðíîé îñîáåííîñòüþ êîòîðûõ ÿâëÿåòñÿ íåîáõîäèìîñòü èñ-ïîëüçîâàíèÿ ñòàíäàðòíûõ îáðàçöîâ (ÑÎ).  íàñòîÿ-ùåå âðåìÿ ìåòîä ßÌÐ-ñïåêòðîñêîïèè íå òîëüêî äî-ïîëíÿåò òðàäèöèîííûå ìåòîäû àíàëèòè÷åñêîãî êîí-òðîëÿ ËÑ, íî è ñ óñïåõîì ìîæåò èõ çàìåíÿòü, ðåøàÿ òå æå çàäà÷è áîëåå ýôôåêòèâíî, ïîçâîëÿÿ îñóùåñòâëÿòü

òîíêèå ñòðóêòóðíûå èññëåäîâàíèÿ, íåäîñòóïíûå ðàíåå.

Öåëü äàííîé ðàáîòû — ïîêàçàòü âîçìîæíîñòü ïðèìåíåíèÿ ìåòîäà ßÌÐ-ñïåêòðîñêîïèè â ôàðìàêî-ïåéíîì àíàëèçå.

Ìíîãîîáðàçèå ñòðóêòóðíîé è àíàëèòè÷åñêîé èí-ôîðìàöèè, ñîäåðæàùåéñÿ â ñïåêòðàõ ßÌÐ, ïîçâîëÿåò èñïîëüçîâàòü ìåòîä ßÌÐ-ñïåêòðîñêîïèè äëÿ ïðîâå-äåíèÿ êà÷åñòâåííîãî è êîëè÷åñòâåííîãî àíàëèçà ôàðìàöåâòè÷åñêèõ ñóáñòàíöèé áåç èñïîëüçîâàíèÿ ÑÎ. Ïî ñðàâíåíèþ ñ äðóãèìè àíàëèòè÷åñêèìè ìåòî-äàìè ìåòîä ßÌÐ èìååò ðÿä ïðåèìóùåñòâ, ÷òî ïîçâî-ëÿåò ñ÷èòàòü åãî ïðèìåíåíèå â ôàðìàêîïåéíîì àíà-ëèçå ïîëíîñòüþ ýêîíîìè÷åñêè îïðàâäàííûì:

1) íå òðåáóåò èñïîëüçîâàíèÿ ýòàëîíîâ è âíóòðåí-íèõ ñòàíäàðòîâ ïðè óñòàíîâëåíèè ïîäëèííîñòè, òàê êàê ðåøàåò çàäà÷ó èäåíòèôèêàöèè ñîåäèíåíèÿ íà-ïðÿìóþ, ïóòåì îïðåäåëåíèÿ ñîñòàâà, ñòðîåíèÿ è ïðî-ñòðàíñòâåííîé ñòðóêòóðû ñîåäèíåíèÿ;

2) ÿâëÿåòñÿ àáñîëþòíûì êîëè÷åñòâåííûì ìåòî-äîì, ïîýòîìó íå òðåáóåò èñïîëüçîâàíèÿ ñòàíäàðòîâ ïðè êîëè÷åñòâåííûõ èçìåðåíèÿõ;

3) íå ðàçðóøàåò èññëåäóåìûé îáðàçåö, ïîçâîëÿÿ óñòàíîâèòü ñòðîåíèå ïðèìåñåé â îáúåêòå èññëåäîâà-íèÿ, êîëè÷åñòâåííî îïðåäåëèòü èõ ñîäåðæàíèå, âû-ÿâèòü ñûðüåâóþ è òåõíîëîãè÷åñêóþ ïðåäûñòîðèþ;

4) íå òðåáóåò ñëîæíîé ïðîáîïîäãîòîâêè, îòëè÷à-åòñÿ âûñîêîé ïðîèçâîäèòåëüíîñòüþ ïðè íåáîëüøîì ðàñõîäå ðåàêòèâîâ;

5) îñîáåííîñòè àãðåãàòíîãî ñîñòîÿíèÿ, äèñïåðñ-íîñòü, ýëåìåíòíûé ñîñòàâ, ìîëåêóëÿðíî-ìàññîâîå ðàñïðåäåëåíèå è äðóãèå õàðàêòåðèñòèêè ñèñòåìû íå ïðåïÿòñòâóþò ïîëó÷åíèþ ñïåêòðîâ ßÌÐ.

Ïðîáîïîäãîòîâêà â ðàìêàõ ìåòîäà ßÌÐ î÷åíü ïðîñòà è çàêëþ÷àåòñÿ â ðàñòâîðåíèè ïðåïàðàòà â ïîä-õîäÿùåì äåéòåðèðîâàííîì ðàñòâîðèòåëå (êàê ïðàâè-ëî, èñïîëüçóåòñÿ íå áîëåå 0,5–0,7 ìë ðàñòâîðèòåëÿ).

Ïðèãîòîâëåííûé ðàñòâîð ìîæíî èñïîëüçîâàòü äëÿ ðåøåíèÿ áîëüøèíñòâà õèìèêî-àíàëèòè÷åñêèõ çàäà÷

ôàðìàêîëîãè÷åñêîé ýêñïåðòèçû (ïîäòâåðæäåíèå ÑÒÀÍÄÀÐÒÈÇÀÖÈßÈÊÎÍÒÐÎËÜÊÀ×ÅÑÒÂÀËÅÊÀÐÑÒÂÅÍÍÛÕÑÐÅÄÑÒÂ

ïîäëèííîñòè, èäåíòèôèêàöèÿ è êîëè÷åñòâåííîå îï-ðåäåëåíèå ïðèìåñåé è îñòàòî÷íûõ îðãàíè÷åñêèõ ðàñ-òâîðèòåëåé, ñîäåðæàíèå îñíîâíîãî êîìïîíåíòà è ò.ä.).

Çàäà÷à ïîäòâåðæäåíèÿ ïîäëèííîñòè ðåøàåòñÿ íà-ïðÿìóþ ïóòåì îïðåäåëåíèÿ ñîñòàâà, ñòðîåíèÿ è ïðî-ñòðàíñòâåííîé ñòðóêòóðû ñîåäèíåíèÿ, ïðè ýòîì ôèê-ñèðóåòñÿ íàëè÷èå îïðåäåëåííûõ ñòðóêòóðíûõ ôðàã-ìåíòîâ è ïîñëåäîâàòåëüíîñòü èõ ñîåäèíåíèÿ äðóã ñ äðóãîì â ìîëåêóëå.  ñëó÷àå, êîãäà èäåíòèôèöèðî-âàòü êîíêðåòíîå ñòðîåíèå àêòèâíîãî êîìïîíåíòà ËÑ íåâîçìîæíî (íàïðèìåð, àêòèâíûé êîìïîíåíò ÿâëÿ-åòñÿ ïîëèìåðîì íåðåãóëÿðíîãî ñòðîåíèÿ è íå èìååò êîíêðåòíîé îáùåé ôîðìóëû) èñïîëüçóþò ñïåêòðû ßÌÐ öåëèêîì, êàê «îòïå÷àòîê ïàëüöà» îáúåêòà. Êàê ïðàâèëî, ïðåäïî÷òåíèå îòäàþò óãëåðîäíûì ñïåê-òðàì, ïîñêîëüêó â ñïåêòðàõ ¹³C ïðàêòè÷åñêè íå íà-áëþäàåòñÿ ïåðåêðûâàíèÿ ñèãíàëîâ âñëåäñòâèå áîëåå øèðîêîãî äèàïàçîíà õèìè÷åñêèõ ñäâèãîâ¹³C. Êðîìå òîãî, ñïåêòðû¹³C ïîçâîëÿþò îïðåäåëÿòü ñîäåðæàíèå

÷åòâåðòè÷íûõ óãëåðîäíûõ àòîìîâ è ôóíêöèîíàëüíûõ ãðóïï, íå ñîäåðæàùèõ ïðîòîíû. Ñëåäóåò îòìåòèòü,

÷òî ïðè îòñóòñòâèè êàêîé-ëèáî èíôîðìàöèè î ñòðóê-òóðíîé èíòåðïðåòàöèè äàííûõ îäíîìåðíûõ ñïåêòðîâ (ßÌÐ ¹H è ¹³C) äîïîëíèòåëüíî ðåãèñòðèðóþò ðÿä êîððåëÿöèîííûõ ñïåêòðîâ (COSY, HSQC, HMQS, HMBC, CIGAR, INADEQUATE è ò.ä.) è ñïåêòðîâ ñ ïåðåíîñîì íàìàãíè÷åííîñòè (DEPT, INEPT è ò.ä.). Ñ èõ ïîìîùüþ òî÷íî îïðåäåëÿþòñÿ ñèñòåìû ñïèí-âçàèìîäåéñòâóþùèõ ÿäåð, èäåíòèôèöèðóþòñÿ ñèãíàëû ïåðåêðûâàþùèõñÿ ïðîòîííûõ ìóëüòèïëå-òîâ, óñòàíàâëèâàþòñÿ âçàèìíîå ñîîòíåñåíèå ñèãíà-ëîâ¹H è¹³C êîíêðåòíûõ óãëåâîäîðîäíûõ ôðàãìåíòîâ è ïîñëåäîâàòåëüíîñòü ñîåäèíåíèÿ ðàçëè÷íûõ ñòðóê-òóðíûõ ôðàãìåíòîâ â ìîëåêóëå.  äàëüíåéøåì, äëÿ èäåíòèôèêàöèè ñîåäèíåíèé, äëÿ êîòîðûõ óæå ïðîâå-äåíà ñòðóêòóðíàÿ èíòåðïðåòàöèÿ ñïåêòðàëüíûõ äàí-íûõ, ïðîâåäåíèå äâóìåðíûõ ýêñïåðèìåíòîâ íåîáÿçà-òåëüíî. Ýôôåêòèâíîñòü èñïîëüçîâàíèÿ ìåòîäà ßÌÐ-ñïåêòðîñêîïèè ïðè èäåíòèôèêàöèè ôàðìàöåâ-òè÷åñêèõ ñóáñòàíöèé ïîêàçàíà â ëèòåðàòóðå [5–8].

Ïðèìåíåíèå ßÌÐ-ñïåêòðîñêîïèè â êîëè÷åñò-âåííîì àíàëèçå îñíîâàíî íà ïðÿìîé ïðîïîðöèîíàëü-íîñòè ìîëÿðíîé êîíöåíòðàöèè ìàãíèòíî-àêòèâíûõ ÿäåð èíòåãðàëüíîé èíòåíñèâíîñòè ñîîòâåòñòâóþùåãî ñèãíàëà ïîãëîùåíèÿ â ñïåêòðå. Ïðè êîëè÷åñòâåííîì îïðåäåëåíèè ëþáîãî êîìïîíåíòà ôàðìàöåâòè÷åñêèõ ñóáñòàíöèé (êàê îñíîâíîãî, òàê è ïðèìåñíîãî) äîñòà-òî÷íî ñîïîñòàâëåíèÿ ïðèâåäåííîé èíòåãðàëüíîé èí-òåíñèâíîñòè ñèãíàëà äàííîãî êîìïîíåíòà ê ñóììå ïðèâåäåííûõ èíòåãðàëüíûõ èíòåíñèâíîñòåé ñèãíà-ëîâ âñåõ êîìïîíåíòîâ ôàðìàöåâòè÷åñêèõ ñóáñòàíöèé [9, 10].  ðàìêàõ ìåòîäà ßÌÐ çàäà÷è ïîäòâåðæäåíèÿ ïîäëèííîñòè, èäåíòèôèêàöèè è êîëè÷åñòâåííîãî îïðåäåëåíèÿ ïðèìåñåé (âêëþ÷àÿ îñòàòî÷íûå

îðãàíè-÷åñêèå ðàñòâîðèòåëè), ðåøàþòñÿ ïàðàëëåëüíî, íà îñ-íîâå èñïîëüçîâàíèÿ îäíîé ïðîáû îáðàçöà, áåç ïðèãî-òîâëåíèÿ ñåðèè êàëèáðîâî÷íûõ ðàñòâîðîâ ÑÎ ïðèìå-ñåé è îñòàòî÷íûõ ðàñòâîðèòåëåé.

Øèðîêî ðàñïðîñòðàíåííûì çàáëóæäåíèåì ÿâëÿ-þòñÿ ïðåäñòàâëåíèÿ îá èñêëþ÷èòåëüíî íèçêîé ÷óâñò-âèòåëüíîñòè ìåòîäà ßÌÐ, îãðàíè÷èâàþùåé åãî

èñ-ïîëüçîâàíèå ïðè êîíòðîëå ïðèìåñåé ËÑ. Àïïàðàòóð-íûå âîçìîæíîñòè ñîâðåìåííûõ èìïóëüñíûõ ßÌÐ-ñïåêòðîìåòðîâ ñî ñâåðõïðîâîäÿùèìè ìàãíèòà-ìè ïîçâîëÿþò ôèêñèðîâàòü ïðèìåñè íà óðîâíå ñîòûõ äîëåé ïðîöåíòà [11], â òî âðåìÿ êàê íîðìàòèâíûå äî-êóìåíòû, êàê ïðàâèëî, óñòàíàâëèâàþò ìàêñèìàëüíî äîïóñòèìûå êîíöåíòðàöèè ïðèìåñíûõ êîìïîíåíòîâ íà óðîâíå 0,1–0,5 âåñîâûõ %.  îòëè÷èå îò òðàäèöè-îííûõ õðîìàòîãðàôè÷åñêèõ ìåòîäîâ, ìåòîä ßÌÐ ïî-çâîëÿåò ôèêñèðîâàòü âñå ïðèìåñè, ïðèñóòñòâóþùèå â àíàëèçèðóåìîì îáðàçöå, â òî âðåìÿ êàê õðîìàòîãðà-ôè÷åñêèå ìåòîäû — òîëüêî òå ïðèìåñè, êîòîðûå íàáëþäàþòñÿ ïðè âûáðàííûõ óñëîâèÿõ õðîìàòîãðà-ôèðîâàíèÿ.

Òî÷íîñòü èíòåãðèðîâàíèÿ ñèãíàëà â ñïåêòðå ßÌÐ, ïðè ïðîâåäåíèè êîëè÷åñòâåííûõ èçìåðåíèé, çàâèñèò òîëüêî îò ñîîòíîøåíèÿ «ñèãíàë : øóì» (S/N):

u I( )% , S N

=0 25+ 100 ,/

ãäå u(I) — ñòàíäàðòíàÿ íåîïðåäåëåííîñòü èíòåãðè-ðîâàíèÿ.

Äëÿ òîãî, ÷òîáû íåîïðåäåëåííîñòü èíòåãðèðîâà-íèÿ íå ïðåâûøàëà 1 %, âåëè÷èíàS/Níå äîëæíà áûòü íèæå 150 [12–14].

Ñïåêòðîñêîïèÿ ßÌÐ ¹³C ìàëîýôôåêòèâíà ïðè èäåíòèôèêàöèè è êîëè÷åñòâåííîì îïðåäåëåíèè ìèêðîïðèìåñåé. Ýòî ñâÿçàíî ñ íèçêîé ÷óâñòâèòåëü-íîñòüþ ìåòîäà ¹³C-ßÌÐ, ïîýòîìó çàäà÷è êîëè÷åñò-âåííîãî îïðåäåëåíèÿ ïðèìåñåé ðåøàþò ñ ïîìîùüþ ìåòîäà ¹H-ßÌÐ, êîòîðûé â 100 ðàç ÷óâñòâèòåëüíåå ìåòîä๳C-ßÌÐ.

Âîçìîæíîñòè ìåòîäà ßÌÐ-ñïåêòðîñêîïèè ïî-çâîëÿþò îïðåäåëÿòü êîëè÷åñòâåííûå õàðàêòåðèñòèêè ïîëèñàõàðèäîâ (ãèäðîêñèýòèëêðàõìàëû, ïóëëóëàíû, äåêñòðàíû) â õîäå ïðîâåäåíèÿ ôàðìàêîïåéíîãî àíà-ëèçà. Îñîáîå âíèìàíèå ïðè ýòîì óäåëÿåòñÿ îïðåäåëå-íèþ ïàðàìåòðîâ ìîëåêóëÿðíî-ìàññîâîãî ðàñïðåäåëå-íèÿ (ÌÌÐ). Îñíîâíûìè ïàðàìåòðàìè ÌÌÐ ïîëèìå-ðîâ ÿâëÿþòñÿ ñðåäíÿÿ ìîëåêóëÿðíàÿ ìàññà (ÌÌ) è èíäåêñ ïîëèäèñïåðñíîñòè, îòðàæàþùèé ñòàòèñòè÷å-ñêóþ øèðèíó ÌÌÐ è ïîçâîëÿþùèé îöåíèòü ðàçáðîñ ìàêðîìîëåêóë ïî ìîëåêóëÿðíûì ìàññàì. Ìåòîäû òðàäèöèîííîé ßÌÐ-ñïåêòðîñêîïèè íåïðèìåíèìû äëÿ îïðåäåëåíèÿ ÌÌ ïîëèìåðîâ. Íàèáîëåå ïåðñïåê-òèâåí â ýòîì íàïðàâëåíèè ìåòîä äèôôóçèîííî-óïî-ðÿäî÷åííîé ñïåêòðîñêîïèè ßÌÐ (Diffusion Ordered Spectroscopy, DOSY), ïîçâîëÿþùèé èçìåðèòü äèô-ôóçèþ ðàçëè÷íûõ ìîëåêóëÿðíûõ îáúåêòîâ (ìîëåêóë, ìàêðîìîëåêóë, ìîëåêóëÿðíûõ êîìïëåêñîâ, ñóïðàìî-ëåêóëÿðíûõ ñèñòåì) ïîä äåéñòâèåì ãðàäèåíòà ìàã-íèòíîãî ïîëÿ [15–17]. Ìåòîä DOSY îñíîâàí íà ðåãè-ñòðàöèè ïîòåðè ôàçîâîé êîãåðåíòíîñòè ÿäåðíûõ ñïè-íîâ çà ñ÷åò òðàíñëÿöèîííûõ ïåðåìåùåíèé ìîëåêóë â òàêîì ïîëå [16, 17]. Äèôôóçíóþ èíôîðìàöèþ èñ-ïîëüçóþò äëÿ êîëè÷åñòâåííîé îöåíêè ðàçìåðà ìàê-ðîìîëåêóë ïîëèìåðà è, ñîîòâåòñòâåííî, åãî ìîëåêó-ëÿðíîé ìàññû [18–24].  ëèòåðàòóðå [25–29] ïîêàçàíà âîçìîæíîñòü îïðåäåëåíèÿ ïàðàìåòðîâ ÌÌÐ ôàðìà-Ñ. Â. Ìîèñååâ, Â. È. Êðûëîâ, Í. Å. Êóçüìèíà, Â. À. ßøêèð, Â. À. Ìåðêóëîâ

ÑÒÀÍÄÀÐÒÈÇÀÖÈßÈÊÎÍÒÐÎËÜÊÀ×ÅÑÒÂÀËÅÊÀÐÑÒÂÅÍÍÛÕÑÐÅÄÑÒÂ

öåâòè÷åñêèõ ñóáñòàíöèé ïîëèñàõàðèäîâ ñ èñïîëüçî-âàíèåì ìåòîäà DOSY ßÌÐ.

Ïðè àíàëèçå ãèäðîêñèýòèëêðàõìàëîâ íåîáõîäè-ìî ó÷èòûâàòü òàêæå ñòåïåíü íåîáõîäè-ìîëÿðíîãî çàìåùåíèÿ (ÌÇ) — îòíîøåíèå êîëè÷åñòâà ãèäðîêñèýòèëüíûõ ãðóïï ê îáùåìó êîëè÷åñòâó a-D-Glcp ôðàãìåíòîâ.

 îòëè÷èå îò õðîìàòîãðàôè÷åñêèõ ìåòîäîâ àíàëèçà èñïîëüçîâàíèå ìåòîäà ßÌÐ ¹H ïîçâîëÿåò ïîâûñèòü òî÷íîñòü îïðåäåëåíèÿ ÌÇ è íå òðåáóåò ïîñòðîåíèÿ ãðàäóèðîâî÷íîé ôóíêöèè ñ èñïîëüçîâàíèåì ñòàí-äàðòíîãî îáðàçöà [30, 31].

ÇÀÊËÞ×ÅÍÈÅ

Ñïåêòðîñêîïèÿ ßÌÐ èìååò íà ñåãîäíÿøíèé äåíü íàèáîëåå áîãàòûé è óñïåøíûé îïûò óñòàíîâëåíèÿ êàê õèìè÷åñêîé ñòðóêòóðû èíäèâèäóàëüíûõ

îðãàíè-÷åñêèõ ñîåäèíåíèé, òàê è äåòàëåé èõ ýëåêòðîííîãî è ïðîñòðàíñòâåííîãî ñòðîåíèÿ. Ïðîöåäóðà ðåãèñòðà-öèè ñïåêòðîâ ßÌÐ, ñáîðà è îáðàáîòêè èíôîðìàðåãèñòðà-öèè ëåãêî ìîæåò áûòü îñóùåñòâëåíà â àâòîìàòè÷åñêîì ðå-æèìå. Âûïîëíåíèå êîëè÷åñòâåííûõ èçìåðåíèé íà îñíîâå äàííûõ ßÌÐ íå òðåáóåò ïðè ðåãèñòðàöèè ñïåêòðîâ èñïîëüçîâàíèÿ ýòàëîíîâ è âíóòðåííèõ ñòàíäàðòîâ, òàê êàê îñíîâàíî íà ñòåõèîìåòðè÷åñêèõ îòíîøåíèÿõ. Âñå ïåðå÷èñëåííîå äåëàåò ìåòîä ßÌÐ óíèâåðñàëüíûì ñðåäñòâîì äëÿ êîìïëåêñíîãî ðåøå-íèÿ õèìèêî-àíàëèòè÷åñêèõ çàäà÷ ïðè ïðîâåäåíèè ôàðìàöåâòè÷åñêîé ýêñïåðòèçû.

ËÈÒÅÐÀÒÓÐÀ

1. Ãîñóäàðñòâåííàÿ ôàðìàêîïåÿ Ðîññèéñêîé Ôåäåðàöèè. 12-å èçä. Ì.: Íàó÷íûé öåíòð ýêñïåðòèçû ñðåäñòâ ìåäèöèíñêîãî ïðè-ìåíåíèÿ; 2008. Ñ. 73–78.

2. European Pharmacopeia 7.2. 2010. V. 1. P. 52–54.

3. United States Pharmacopeia 30-National Formulary 25. 761. Nuc-lear Magnetic Resonance. P. 324–31.

4. The Japanese Pharmacopoeia. 2006. 2.21. Nuclear Magnetic Reso-nance Spectroscopy. P. 38–39.

5. Êóçüìèíà ÍÅ, Ìîèñååâ ÑÂ, ßøêèð ÂÀ, Ìåðêóëîâ ÂÀ. Èñïîëüçî-âàíèå ìåòîäà ßÌÐ-ñïåêòðîñêîïèè äëÿ ïîäòâåðæäåíèÿ ïîä-ëèííîñòè è îöåíêè êà÷åñòâà ñóáñòàíöèé àçèòðîìèöèíà. Âåäî-ìîñòè Íàó÷íîãî öåíòðà ýêñïåðòèçû ñðåäñòâ ìåäèöèíñêîãî ïðè-ìåíåíèÿ 2012; (1): 10–14.

6. Êóçüìèíà ÍÅ, Ìîèñååâ ÑÂ, ßøêèð ÂÀ, Ìåðêóëîâ ÂÀ. Èñïîëüçî-âàíèå ìåòîäà ßÌÐ-ñïåêòðîñêîïèè äëÿ ïîäòâåðæäåíèÿ ïîä-ëèííîñòè, èäåíòèôèêàöèè è êîëè÷åñòâåííîãî îïðåäåëåíèÿ ïî-ñòîðîííèõ ïðèìåñåé ñóáñòàíöèè ðóòèíà. Âåäîìîñòè Íàó÷íîãî öåíòðà ýêñïåðòèçû ñðåäñòâ ìåäèöèíñêîãî ïðèìåíåíèÿ 2012;

(3): 14–18.

7. Êóçüìèíà ÍÅ, Ìîèñååâ ÑÂ, ßøêèð ÂÀ. Èñïîëüçîâàíèå ìåòîäà ìóëüòèÿäåðíîé ßÌÐ-ñïåêòðîñêîïèè äëÿ îïðåäåëåíèÿ êà÷åñò-âà ëåêàðñòâåííûõ ñóáñòàíöèé. Âåäîìîñòè Íàó÷íîãî öåíòðà ýê-ñïåðòèçû ñðåäñòâ ìåäèöèíñêîãî ïðèìåíåíèÿ 2012; (4): 4–10.

8. Ìîèñååâ ÑÂ, Êðûëîâ ÂÈ, Ìàñòåðêîâà ÒÂ, ßøêèð ÂÀ, Áóíÿòÿí ÍÄ. Èñïîëüçîâàíèå ìåòîäà ßÌÐ-ñïåêòðîñêîïèè äëÿ ïîäòâåð-æäåíèÿ ïîäëèííîñòè, èäåíòèôèêàöèè è êîëè÷åñòâåííîãî îïðåäåëåíèÿ ïîñòîðîííèõ ïðèìåñåé ñóáñòàíöèè ñàëèöèëîâîé êèñëîòû. Âåäîìîñòè Íàó÷íîãî öåíòðà ýêñïåðòèçû ñðåäñòâ ìå-äèöèíñêîãî ïðèìåíåíèÿ 2014; (1): 15–19.

9. Ãþíòåð Õ. Ââåäåíèå â êóðñ ñïåêòðîñêîïèè ßÌÐ. Ì.: Ìèð; 1984.

10. Êàëàáèí ÃÀ, Êàíèöêàÿ ËÂ, Êóøíàðåâ ÄÔ. Êîëè÷åñòâåííàÿ ñïåê-òðîñêîïèÿ ßÌÐ ïðèðîäíîãî îðãàíè÷åñêîãî ñûðüÿ è ïðîäóêòîâ åãî ïåðåðàáîòêè. Ì.: Õèìèÿ; 2000.

11. Êóçüìèíà ÍÅ, Ìîèñååâ ÑÂ, Êðûëîâ ÂÈ, ßøêèð ÂÀ, Ìåðêóëîâ ÂÀ.

Âîçìîæíîñòè ìåòîäà ßÌÐ-ñïåêòðîñêîïèè ïðè îïðåäåëåíèè ìèêðîêîìïîíåíòîâ ñìåñåé. Æóðíàë àíàëèòè÷åñêîé õèìèè 2014;

69(11): 1152–60.

12. Malz F, Jancke Í. Validation of quantitative NMR. J Pharm Biomed Anal. 2005;38(5): 813–23.

13. Malz F. Quantitative NMR-Spektroscopie als Referenzverfahren in der analytischen Chemie. Dissertation. Berlin: HumboldtÛniversität;

2003.

14. Crouch R, Russell D. Easy, precise and accurate quantitative NMR.

Application note. Santa Clara: Agilent Technologies Inc. USA; 2011.

15. Morris KF., Johnson Jr. CS. Resolution of discrete and continuous molecular size distributions by means of diffusion-ordered 2D NMR spectroscopy. J Am Chem Soc. 1993; 115(10): 4291–99.

16. Price WS. Pulsed-field gradient NMR as a tool for studying translatio-nal diffusion. Part I. Basic theory. Concepts Magn Reson. 1997; 9:

299–336.

17. Price WS. Pulsed-field gradient nuclear magnetic resonance as a tool for studying translational diffusion. Part 2. Experimental aspects.

Concepts Magn. Reson. 1998; 10: 197–237.

18. Li W, Chung H, Daeffler C, Johnson JA, Grubbs RH. Application of (1)H DOSY for Facile Measurement of Polymer Molecular Weights.

Macromolecules2012;45(24): 9595–603.

19. Mazarin M, Viel S, Allard-Breton B, Thevand A, Charles L. Use of Pul-sed Gradient Spin?Echo NMR as a Tool in MALDI Method Develop-ment for Polymer Molecular Weight Determination. Anal Chem.

2006;78(8): 2758–64.

20. Viel S, Capitani D, Mannina L, Segre A. Diffusion-ordered NMR spect-roscopy: a versatile tool for the molecular weight determination of uncharged polysaccharides. Biomacromolecules 2003;4(6): 1843–7.

21. Tomati U, Belardinelli M, Galli E, Ior V, Capitani D, Mannina L, Viel S, Segre A. NMR characterization of the polysaccharidic fraction from Lentinula edodes grown on olive mill waste waters. Carbohydr Res.

2004;339(6): 1129–34.

22. Politi M, Groves P, Chavez MI, Canada FJ, Jimenez-Barbero J. Useful applications of DOSY experiments for the study of mushroom poly-saccharides. Carbohydr Res. 2006;341(1): 84–9.

23. Suarez ER, Syvitski R, Kralovec JA, Noseda MD, Barrow CJ, Ewart HS, Lumsden MD, Grindley TB. Immunostimulatory polysaccharides from Chlorella pyrenoidosa. A new galactofuranan. measurement of molecular weight and molecular weight dispersion by DOSY NMR.

Biomacromolecules 2006;7(8): 2368–76.

24. Maina NH. Structure and macromolecular properties ofWeissella confusaandLeuconostoc citreumdextrans with a potential applicati-on in sourdough. Ph. D. Dis. Helsinki: University of Helsinki; 2012.

25. Êóçüìèíà ÍÅ, Ìîèñååâ ÑÂ, Êðûëîâ ÂÈ, ßøêèð ÂÀ, Ìåðêóëîâ ÂÀ.

Âîçìîæíîñòè ïðèìåíåíèÿ ìåòîäà äèôôóçíî-óïîðÿäî÷åííîé ñïåêòðîñêîïèè ßÌÐ äëÿ êîëè÷åñòâåííîé îöåíêè ñðåäíåé ìîëå-êóëÿðíîé ìàññû ïîëóëëàíîâ. Âåäîìîñòè Íàó÷íîãî öåíòðà ýêñ-ïåðòèçû ñðåäñòâ ìåäèöèíñêîãî ïðèìåíåíèÿ 2013; (4): 8–11.

26. Ìîèñååâ ÑÂ, Êóçüìèíà ÍÅ, Êðûëîâ ÂÈ, ßøêèð ÂÀ, Ìåðêóëîâ ÂÀ.

Îïðåäåëåíèå ïàðàìåòðîâ ìîëåêóëÿðíî-ìàññîâîãî ðàñïðåäåëå-íèÿ äåêñòðàíîâ ìåòîäîì äèôôóçèîííî-óïîðÿäî÷åííîé ñïåêòðî-ñêîïèè ßÌÐ. Âåäîìîñòè Íàó÷íîãî öåíòðà ýêñïåðòèçû ñðåäñòâ ìå-äèöèíñêîãî ïðèìåíåíèÿ 2014; (2): 9–15.

27. Êóçüìèíà ÍÅ, Ìîèñååâ ÑÂ, Êðûëîâ ÂÈ, ßøêèð ÂÀ, Ìåðêóëîâ ÂÀ.

Êîëè÷åñòâåííîå îïðåäåëåíèå ñðåäíåé ìîëåêóëÿðíîé ìàññû äåêñòðàíîâ ìåòîäîì äèôôóçíî-óïîðÿäî÷åííîé ñïåêòðîñêîïèè ßÌÐ. Æóðíàë àíàëèòè÷åñêîé õèìèè 2014; 69(10): 1047–53.

28. Êóçüìèíà ÍÅ, Ìîèñååâ ÑÂ, Êðûëîâ ÂÈ, ßøêèð ÂÀ, Ìåðêóëîâ ÂÀ.

Îïðåäåëåíèå ñðåäíåé ìîëåêóëÿðíîé ìàññû ãèäðîêñèýòèëêðàõ-ìàëîâ ìåòîäîì äèôôóçèîííî-óïîðÿäî÷åííîé ñïåêòðîñêîïèè ßÌÐ. Æóðíàë àíàëèòè÷åñêîé õèìèè 2015; 70(1): 30–36.

29. Êóçüìèíà ÍÅ, Ìîèñååâ ÑÂ, Êðûëîâ ÂÈ, ßøêèð ÂÀ, Ìåðêóëîâ ÂÀ.

Îïðåäåëåíèå ïàðàìåòðîâ ìîëåêóëÿðíî-ìàññîâîãî ðàñïðåäåëå-Èñïîëüçîâàíèå ìåòîäà ßÌÐ-ñïåêòðîñêîïèè â ôàðìàêîïåéíîì àíàëèçå

ÑÒÀÍÄÀÐÒÈÇÀÖÈßÈÊÎÍÒÐÎËÜÊÀ×ÅÑÒÂÀËÅÊÀÐÑÒÂÅÍÍÛÕÑÐÅÄÑÒÂ

íèÿ ãèäðîêñèýòèëêðàõìàëîâ ìåòîäîì

äèôôóçèîííî-óïîðÿäî-÷åííîé ñïåêòðîñêîïèè ßÌÐ. Æóðíàë àíàëèòè÷åñêîé õèìèè 2015;

70(7): 727–33.

30. Ïðîêîôüåâ ÅÏ, Þðèí ÎÀ. Îïðåäåëåíèå ñòåïåíè çàìåùåíèÿ è ìîëÿðíîãî çàìåùåíèÿ â îêñèýòèëèðîâàííûõ êðàõìàëàõ

ìåòî-äîì ßÌйH. Õèìèêî-ôàðìàöåâòè÷åñêèé æóðíàë 1990; 24(7):

82–84.

31. Êóçüìèíà ÍÅ, Ìîèñååâ ÑÂ, Êðûëîâ ÂÈ, ßøêèð ÂÀ, Ìåðêóëîâ ÂÀ.

Ìîäèôèêàöèÿ ìåòîäèêè îïðåäåëåíèÿ ìîëÿðíîãî çàìåùåíèÿ ãèäðîêñèýòèëêðàõìàëîâ ìåòîäîì¹H ßÌÐ ñïåêòðîñêîïèè. Õèìè-êî-ôàðìàöåâòè÷åñêèé æóðíàë 2015;49(8): 44–48.

ÎÁ ÀÂÒÎÐÀÕ

Ôåäåðàëüíîå ãîñóäàðñòâåííîå áþäæåòíîå ó÷ðåæäåíèå «Íàó÷íûé öåíòð ýêñïåðòèçû ñðåäñòâ ìåäèöèíñêîãî ïðèìåíåíèÿ» Ìèíèñòåðñòâà çäðàâîîõðàíåíèÿ Ðîññèéñêîé Ôåäåðàöèè. Ðîññèéñêàÿ Ôåäåðàöèÿ, 127051, Ìîñêâà, Ïåòðîâñêèé áóëüâàð, 8, ñòð. 2.

Ìîèñååâ Ñåðãåé Âëàäèìèðîâè÷.Ýêñïåðò 1-é êàòåãîðèè ëàáîðàòîðèè íàíîëåêàðñòâ, ïðåïàðàòîâ äëÿ êëåòî÷íîé è ãåíîòåðàïèè, êàíä. õèì. íàóê.

Êóçüìèíà Íàòàëèÿ Åâãåíüåâíà.Âåäóùèé ýêñïåðò ëàáîðàòîðèè íàíîëåêàðñòâ, ïðåïàðàòîâ äëÿ êëåòî÷íîé è ãåíîòåðàïèè, ä-ð õèì. íàóê.

Êðûëîâ Âëàäèñëàâ Èãîðåâè÷.Âåäóùèé èíæåíåð ëàáîðàòîðèè íàíîëåêàðñòâ, ïðåïàðàòîâ äëÿ êëåòî÷íîé è ãåíîòåðàïèè.

ßøêèð Âàäèì Àíàòîëüåâè÷.Íà÷àëüíèê ëàáîðàòîðèè íàíîëåêàðñòâ, ïðåïàðàòîâ äëÿ êëåòî÷íîé è ãåíîòåðàïèè, êàíä. õèì. íàóê.

Ìåðêóëîâ Âàäèì Àíàòîëüåâè÷.Çàìåñòèòåëü ãåíåðàëüíîãî äèðåêòîðà ïî ýêñïåðòèçå ëåêàðñòâåííûõ ñðåäñòâ, ä-ð ìåä. íàóê, ïðîô.

ÀÄÐÅÑ ÄËß ÏÅÐÅÏÈÑÊÈ

Ìîèñååâ Ñåðãåé Âëàäèìèðîâè÷; [email protected]

THE USE OF NMR-SPECTROSCOPY IN PHARMACOPOEIAL ANALYSIS S. V. Moiseev, V. I. Krylov, N. E. Kuzmina, V. A. Yashkir, V. A. Merkulov

Federal State Budgetary Institution

«Scientific Centre for Expert Evaluation of Medicinal Products»

of the Ministry of Health of the Russian Federation, 127051, Moscow, Russia

Abstract:The article illustrates the prospects of using nuclear magnetic resonance spectroscopy for complex, fast and reliable determi-nation of key quality attributes of drug substances while performing pharmacopoeial analysis.

Key words:NMR-spectroscopy; pharmacopoeial analysis; structural interpretation of NMR spectra; identification of drug substances;

assay; molar mass distribution; molar substitution.

For citation:Moiseev SV, Krylov VI, Yashkir VA, Merkulov VA. The use of NMR-spectroscopy in pharmacopoeial analysis. The Bul-letin of the Scientific Centre for Expert Evaluation of Medicinal Products 2016; (2): 53–57.

REFERENCES

1. The State Pharmacopoeia of the Russian Federation. 12th ed. Mos-cow: NCESMP; 2008. P. 73–78 (in Russian).

2. European Pharmacopeia 7.2. 2010. V. 1. P. 52–54.

3. United States Pharmacopeia 30-National Formulary 25. 761. Nuc-lear Magnetic Resonance. P. 324–31.

4. The Japanese Pharmacopoeia. 2006. 2.21. Nuclear Magnetic Reso-nance Spectroscopy. P. 38–39.

5. Kuzmina NE, Moiseev SV, Yashkir VA, Merkulov VA. Use of nuclear magnetic resonance spectroscopy method for the identification and quality evaluation of azithromycin substance. Vedomosti Na-uchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya 2012; (1): 10–14 (in Russian).

6. Kuzmina NE, Moiseev SV, Yashkir VA, Merkulov VA. The use of magnetic resonance spectroscopy for authentication, identificati-on and assay of impurites in routine substance. Vedomosti Nauch-nogo tsentra ekspertizy sredstv meditsinskogo primeneniya 2012;

(3): 14–18 (in Russian).

7. Kuzmina NE, Moiseev SV, Yashkir VA. Multinuclear NMR-spectros-copy for drug substances quality assessment. Vedomosti Nauch-nogo tsentra ekspertizy sredstv meditsinskogo primeneniya 2012;

(4): 4–10 (in Russian).

8. Moiseev SV, Krylov VI, Masterkova TV, Yashkir VA, Bunyatyan ND.

Nuclear magnetic resonance spectroscopy for drug identification, characterization and quantification of impurities in substance of salicylic acid. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya 2014; (1): 15–19 (in Russian).

9. Gunter H. NMR Spectroscopy. An Introduction. Moscow: Mir; 1984 (in Russian).

10. Kalabin GA, Kanitskaya LV, Kushnarev DF. Quantitative NMR spect-roscopy of natural organic raw materials and its products. Moscow:

Himiya; 2000 (in Russian).

11. Kuzmina NE, Moiseev SV, Krylov VI, Yashkir VA, Merkulov VA. Featu-res of NMR determination of microcomponents in mixtuFeatu-res. Zhurnal analiticheskoy himii 2014;69(11): 1152–60 (in Russian).

12. Malz F, Jancke Í. Validation of quantitative NMR. J Pharm Biomed Anal. 2005;38(5): 813–23.

13. Malz F. Quantitative NMR-Spektroscopie als Referenzverfahren in der analytischen Chemie. Dissertation. Berlin: HumboldtÛniversität;

2003.

14. Crouch R, Russell D. Easy, precise and accurate quantitative NMR.

Application note. Santa Clara: Agilent Technologies Inc. USA; 2011.

15. Morris KF., Johnson Jr. CS. Resolution of discrete and continuous molecular size distributions by means of diffusion-ordered 2D NMR spectroscopy. J Am Chem Soc. 1993; 115(10): 4291–99.

16. Price WS. Pulsed-field gradient NMR as a tool for studying translatio-nal diffusion. Part I. Basic theory. Concepts Magn Reson. 1997; 9:

299–336.

17. Price WS. Pulsed-field gradient nuclear magnetic resonance as a tool for studying translational diffusion. Part 2. Experimental aspects.

Concepts Magn. Reson. 1998; 10: 197–237.

18. Li W, Chung H, Daeffler C, Johnson JA, Grubbs RH. Application of (1)H DOSY for Facile Measurement of Polymer Molecular Weights.

Macromolecules2012;45(24): 9595–603.

19. Mazarin M, Viel S, Allard-Breton B, Thevand A, Charles L. Use of Pul-sed Gradient Spin?Echo NMR as a Tool in MALDI Method Develop-ment for Polymer Molecular Weight Determination. Anal Chem.

2006;78(8): 2758–64.

20. Viel S, Capitani D, Mannina L, Segre A. Diffusion-ordered NMR spect-roscopy: a versatile tool for the molecular weight determination of uncharged polysaccharides. Biomacromolecules 2003;4(6): 1843–7.

21. Tomati U, Belardinelli M, Galli E, Ior V, Capitani D, Mannina L, Viel S, Segre A. NMR characterization of the polysaccharidic fraction from Lentinula edodes grown on olive mill waste waters. Carbohydr Res.

2004;339(6): 1129–34.

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