| Abstract | Cilj istraživanja
Cilj ovog istraživanja je na osnovi pregleda dostupne literature opisati globalni problem
krivotvorenih lijekova i lijekova koji ne zadovoljavaju standarde kakvoće (eng.
substandard/falsified medical products), s posebnim naglaskom na antimalarike koji su
osobito podložni krivotvorenju. Analiziraju se uzroci i posljedice i opisuju napori koji se
ulažu u suzbijanje tog problema. Opisuje se pojavnost, etiologija, epidemiologija, patogeneza
i klinička slika malarije. Navode se smjernice za prevenciju i liječenje malarije, uključujući
glavne skupine antimalarika na svjetskom tržištu. Pregledno se navode analitičke metode za
otkrivanje krivotvorenih antimalarika i istražuju mogućnosti primjene dvije inovativne
analitičke metode temeljene na Ramanovoj hiperspektralnoj analizi i ELISA
imunoenzimatskim testovima, koje bi u budućnosti mogle postati značajan alat u borbi protiv
krivotvorenja lijekova.
Materijal i metode
Istraživanja u okviru ovog specijalističkog rada teorijskog su karaktera. Literatura je
pretraživana prema temi i predmetu istraživanja, autorima i časopisima. Pretraga je
obuhvaćala stručne i znanstvene članke, relevantne farmakopeje, važeće smjernice i izvještaje
Svjetske zdravstvene organizacije i regulatornih tijela, kao i razne elektroničke izvore. Na
temelju proučavanja navedene literature izvedena su vlastita razmatranja predmetne
problematike.
Pri pretraživanju literature korištene su baze podataka: PubMed, Medline, Science Direct,
ResearchGate, Scopus, Embase, Web of Science.
Rezultati
Do danas je razvijen velik broj inovativnih metoda za otkrivanje krivotvorenih antimalarika,
temeljenih na različitim tehnikama. Metoda temeljena na Ramanovoj spektroskopiji opisana u
ovom radu je jednostavna, jeftina i brza te bi se u budućnosti mogla koristiti za određivanje
sadržaja djelatnih tvari i raspodjelu djelatnih tvari unutar tableta antimalarika Riameta®.
Metoda temeljena na ELISA imunoenzimatskim testovima opisana u ovom radu razvijena je u
obliku testnog štapića, kojim se semikvantitativno može odrediti sadržaj dihidroartemisinina u
različitim antimalaricima na temelju prisutnosti ili odsutnosti testne linije. Metoda je
jednostavna, jeftina, ne zahtijeva kompleksnu obradu uzoraka. Obje metode mogle bi se u
budućnosti koristiti za preliminarno ispitivanje suspektnih antimalarika.
Zaključak
Krivotvorenje lijekova je globalni javnozdravstveni, socijalni i ekonomski problem s
izraženim trendom rasta u posljednjem desetljeću. Antimalarici su grupa lijekova osobito
podložna krivotvorenju. Jedna od specifičnih mjera koje se poduzimaju u cilju suzbijanja
problema krivotvorenja lijekova je poticanje razvoja novih tehnologija i inovativnih
analitičkih metoda za detektiranje i kvantificiranje djelatnih tvari u krivotvorenim lijekovima.
Metode koje se temelje na Ramanovoj hiperspektralnoj analizi te na ELISA
imunoenzimatskim testovima već su se pokazale uspješnima u otkrivanju krivotvorenih
antimalarika na bazi artemisinina. Komparativne prednosti ovih metoda u odnosu na ostale
analitičke metode, kao npr. brzina dobivanja rezultata, fleksibilnost, jednostavnost, efikasnost,
neinvazivnost, cjenovna i ekološka prihvatljivost i slično, otvaraju prostor za uvođenje ovih
inovativnih metoda u postupke preliminarnog detektiranja suspektnog lijeka direktno na
mjestu pronalaska, odnosno uz minimalnu laboratorijsku obradu. |
| Abstract (english) | Objectives
This specialist thesis aims to describe the global problem of falsified and substandard medical
products by using a systematic review of available literature, with special emphasis on
antimalarials that are particularly susceptible to counterfeiting. Firstly, the thesis explains
causes and impacts, as well as the efforts taken to combat this problem. The prevalence,
etiology, pathogenesis, epidemiology, and clinical manifestations of malaria are described.
Guidelines for the prevention and treatment of malaria are given, including the main groups
of antimalarials on the world market. The thesis gives an overview of analytical methods for
the detection of falsified/substandard antimalarials. Finally, implementation possibilities of
two innovative analytical methods are analyzed, one of which is based on Raman
hyperspectral analysis and the other on the monoclonal antibody-based immunoassays
(ELISA), which could be used as a significant tool in confronting this phenomenon in the
future.
Material and Methods
Research within this thesis is theoretical. Literature was searched by the topic, subject of the
research, authors and journals. The literature search included a wide range of specialized and
scientific articles, current versions of pharmacopeias and currently valid guidelines and
reports issued by the World Health Organization and regulatory bodies, as well as various
electronic sources. The author's reflections derive from the study of the mentioned literature.
In the literature search, databases were used: PubMed, Medline, Science Direct, ResearchGate,
Scopus, Embase, Web of Science.
Results
To the date, a large number of innovative methods have been developed for the detection of
falsified antimalarials, based on various analytical techniques. The method based on Raman
spectroscopy described in this thesis is simple, inexpensive and fast, and could be used in the
future for the determination of the content of active substances and the spatial concentration
distribution of active substances within Riamet® antimalarial tablets. The method based on
ELISA immunoassays described in this thesis has been developed in the form of dipstick, and
can be used for semiquantitative determination of the content of dihydroartemisinin in
different antimalarials, based on the presence or absence of the test line. The method is simple,
inexpensive and does not require complex sample processing. Both methods could be used in
the future for preliminary testing of suspicious antimalarials.
Conclusion
The counterfeiting of medical products is a global public health, social and economic problem
with a pronounced growth rate in the last decade. Antimalarials fall into a group of drugs
particularly susceptible to counterfeiting. One of the specific measures for combating the
growing problem of drugs counterfeiting is to encourage the development of innovative
technologies and innovative analytical methods for the detection and quantification of active
pharmaceutical ingredients in counterfeit drugs. The methods which are based on Raman
hyperspectral analysis and the monoclonal antibody-based immunoassays (ELISA) have been
already successful in detecting counterfeit artemisinin-based antimalarials. Comparative
advantages of these methods in contrast to other analytical methods, such as speed of results,
flexibility, simplicity, efficiency, non-invasiveness, cost and environmental acceptability etc.,
open the door to the introduction of these innovative methods in the procedures of preliminary
detection of suspicious drugs directly at the site of discovery, ie with minimal laboratory
processing. |
