| Abstract | Cilj istraživanja: Uporaba zelenih analitičkih metoda još uvijek je ograničena u farmaceutskom području, posebice u aktivnostima kontrole kvalitete. Ozelenjavanje analitičkih metoda postalo je od velikog interesa u području farmaceutske analize kako bi se zaštitilo zdravlje operatera i okoliš. Metode po kojima se ispituju djelatne tvari, dio gotovih lijekova i dr. propisane su farmakopejama, stoga je cilj ovog istraživanja na modelu izabranih djelatnih tvari ispitati koliko su zelene metode za određivanje sadržaja i onečišćenja tih tvari u Europskoj farmakopeji.
Materijal i metode: Vršena je procjena zelenosti metoda opisanih za određivanje sadržaja i onečišćenja za šest lijekova iz skupine imunosupresiva i 5-aminosalicilata, azatioprina, merkaptopurina, mesalazina, sulfasalazina, budesonida i osalazina prema moografijama Europske farmakopeje 10.3. Zelenost opisanih metoda određena je koristeći dva slobodno dostupna alata AGREE i AMGS. Viši AGREE i niži AMGS zbir znače zeleniju metodu. Dobiveni rezultati alata za izračun zelenosti metoda su pojedinačno opisani, a za usporedbu rezultata dvaju alata korišten je test Spearmanove korelacije. Statistička značajnost je postavljena na p < 0,05. Statistička analiza je napravljena koristeći softver MedCalc verzija19.1.2 (MedCalc Software, Ostend, Belgija).
Rezultati: AGREE zbir za metode određivanja sadržaja bio je u rasponu od 0,38 do 0,54 i postizao viši zbir za titrimetrijske metode. AGREE za metode određivanja onečišćenja se kretao od 0,33 do 0,43. Sukladno izračunima prema AGREE može se zaključiti da su metode za određivanje sadržaja aktivne tvari zelenije od onih za određivanje onečišćenja. AMGS zbir za metode onečišćenja je bio u rasponu od 58,63 do 312,07. Metoda za određivanje sadržaja budesonida je postigla 837,93 AMGS zbir. Prema provedenoj statističkoj obradi AGREE i AMGS rezultata za istraživane metode, nije pronađena značajna korelacija među dvama izračunima (r = -0,421; P = 0,226).
Zaključak: Rezultati ovog istraživanja upućuju na zaključak da se postojeće farmakopejske metode za određivanje sadržaja i onečišćenja u djelatnim tvarima ne mogu smatrati zelenima sukladno dostupnim alatima za procjenu ekološke prihvatljivosti analitičkih metoda. |
| Abstract (english) | Objectives: The use of green analytical methods is still limited in the pharmaceutical field, especially in quality control activities. The greening of analytical methods has become of great interest in the field of pharmaceutical analysis in order to protect operator health and the environment. The methods by which active substances, part of finished medicines, etc. are tested are given in pharmacopoeias, therefore the aim of this research is on the examine greenness of methods for determination of assay and impurities in European Pharmacopoeia on a model of selected active substances.
Material and Methods: An assessment of the greenness of the methods for determining assay and impurities of six drugs from the group of immunosuppressants and 5-aminosalicylates was performed, azathioprine, mercaptopurine, mesalazine, sulfasalazine budesonide and osalazine, according to the European Pharmacopoeia 10.3. monographs. The greenness of the described methods was determined using two freely available tools AGREE and AMGS. A higher AGREE and a lower AMGS score mean a greener method. The obtained results of the method's greenness are described individually, and the Spearman rank correlation test was used to compare the results of the two tools. Statistical significance was set at p < 0.05. Statistical analysis was performed using MedCalc software version 19.1.2 (MedCalc Software, Ostend, Belgium).
Results: The AGREE score for assay methods ranged from 0.38 to 0.54 and achieved a higher score for titrimetric methods. AGREE for impurities methods ranged from 0.33 to 0.43. According to the calculations of AGREE, it can be concluded that the methods for determination of assay active substances are greener than those for detection of impurities. The AMGS total score for impurities methods ranged from 58.63 to 312.07. The budesonide assay determination method achieved 837.93 AMGS total score. According to the performed statistical analysis of AGREE and
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AMGS results for the investigated methods, no significant correlation was found between the results of the two calculations (r = -0.421; P = 0.226).
Conclusion: The results of this research point to the conclusion that the existing pharmacopoeial methods for determining the assay and impurities in active substances cannot be considered green according to the available tools for assessing the ecological acceptability of analytical methods. |
