@conference{
author = "Otašević, Biljana and Đajić, Nevena and Golubović, Jelena and Krmar, Jovana and Protić, Ana",
year = "2021",
abstract = "Qualitative and quantitative assessment of drug substances and drug dosage forms is of utmost
importance for the quality control in pharmaceutical industry. Among the analytical techniques
available, high performance liquid chromatography (HPLC) stands out due to its high efficiency and
robustness. But, HPLC is also characterized by high consumption of toxic organic solvents used both for
method development and routine analyses. These solvents could harmfully impact the environment
and human health. Therefore, various strategies are developing for attracting eco-friendly character to
HPLC. Recently introduced green chromatography concept is based on the 3R rule (Reduce – Replace –
Recycle) implying the HPLC method development governed by the decreased use of acetonitrile labeled
as the most commonly used HPLC solvent and its replacement with ethanol or acetone (1). However,
these greener alternatives are known for their high UV absorbtion cut-off values making them
unsuitable for common UV/VIS detection. As appropriate solvent compatible solution, the use of
Corona Charged Aerosol Detector (CAD) is proposed. CAD is recognized as a universal detector
providing persistent mass sensitive analyte response independent of chemical structure (no need for
UV/VIS chromofores or ionization ability). The detection principle involves the nebulization of
chromatographic mobile phase, the evaporation of aerosol droplets and finally the production of
charged analyte particles (2). Assuming that chromatographic behavior and CAD generated responses
of analytes could be affected by various mobile phase related factors and/or detector parameters
settings, design of experiments (DoE) supported HPLC-CAD method development was performed for
the analysis of antipsychotic drug risperidone in presence of its impurities. By carefully planning the
number and the order of performing experiments, DoE methodology enables investigation of
significance effects of multiple factor effects together with their factor interactions. Different
experimental settings involving variation of organic solvent type and content in range 15-25% (V/V),
mobile phase flow rate (0.50-1.00 mL min -1) and column temperature (25-50 °C) were examined in
accordance with Box-Behnken design and selectivity factor between adjacent peaks on the
chromatogram was measured. The optimal conditions were defined applying mucticriteria decision
making approach by means of Derringer desirability function evaluation. Optimal separations were
achieved using 20% (V/V) of ethanol in mobile phase flowing at 0.6 mL min -1 under 37.5 °C column
temperature, while in case of acetone, optimum comprised 17% (V/V) of organic modifier, 0.8 mL min -1
and 37.5 °C. Finally, eco-friendly character of both methods was rated by Green Analytical Procedure
Index, GAPI (3)., Kvalitativna i kvantitativna analiza farmaceutskih supstanci i doziranih oblika predstavlja
činioce od najvećeg značaja za kontrolu kvaliteta u farmaceutskoj industriji. Među dostupnim
analitičkim tehnikama, tečna hromatografija pod visokim pritiskom (HPLC) ističe se svojom visokom
efikasnošć u i robusnošću. Ali, HPLC takođe karakteriše velika potrošnja toksičnih organskih rastvarača
koji se koriste za razvoj metoda i za rutinsku analizu lekova. Ovi rastvarači mogu štetno uticati i na
životnu sredinu i na zdravlje ljudi. Zbog toga se razvijaju različite strategije za obezbeđivanje ekološki
prihvatljivog karaktera HPLC metode. Nedavno predstavljeni koncept zelene hromatografije zasnovan
je na pravilu 3 R (Smanji - Zameni - Recikliraj), što podrazumeva razvoj HPLC metode koji se rukovodi
smanjenom upotrebom acetonitrila kao najčešće korišć enog rastvarača i njegovu zamenu etanolom ili
acetonom (1). Međutim, ove zelenije alternative poznate su po visokim vrednostima za UV apsorpciju,
što ih čini neprikladnim za uobičajenu UV/VIS detekciju. Kao odgovarajuće rešenje kompatibilno sa
pomenutim rastvaračima, predlaže se upotreba detektora naelektrisanja u aerosolu (CAD). CAD je
prepoznat kao univerzalni detektor koji pruža postojan odgovor zavistan od mase analita, a nezavisan
od hemijske strukture (postojanje UV/VIS hromofora ili sposobnosti jonizacije). Princip CAD detekcije
uključuje raspršivanje hromatografske mobilne faze u vidu kapljica aerosola, njihovo isparavanje i
konačno naelektrisavanje dobijenih čestica analita (2). Pretpostavljajuć i da na hromatografsko
ponašanje i CAD generisane odgovore analita mogu uticati različiti faktori povezani sa mobilnom fazom
i/ili parametrima podešavanja detektora, izvršen je razvoj HPLC-CAD metode za analizu antipsihotika
risperidona u prisustvu njegovih nečistoća uz podršku metodologije dizajna eksperimenata (DoE).
Pažljivim planiranjem broja i redosleda izvođenja eksperimenata, DoE omoguć ava ispitivanje značaja
efekata više faktora istovremeno zajedno sa njihovim faktorskim interakcijama. Različite
eksperimentalne postavke koje uključuju varijacije tipa i sadržaja organskog rastvarača u opsegu 15-
25% (V/V), protok mobilne faze (0,50-1,00 mL min -1) i temperaturu kolone (25-50 °C) ispitivane su u
skladu sa Boks-Behnken-ovim dizajnom i faktor selektivnosti između susednih vrhova na
hromatogramu je praćen. Optimalni uslovi definisani su primenom pristupa mutikriterijumskog
odlučivanja baziranog na izračunavanju Derringer-ove funkcije poželjnosti. Optimalna separacija je
postignuta primenom 20% (V/V) etanola u mobilnoj fazi koja teče pri 0,6 mL min -1 i pri temperaturi
kolone od 37,5 °C, dok je u slučaju acetona optimum podrazumevao 17% (V/V) organskog
modifikatora, protok 0,8 mL min -1 i temperaturu 37,5 °C. Konačno, ekološki karakter obe metode
procenjen je na osnovu indeksa zelenih analitičkih procedura, GAPI (3).",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "New strategies in the development of ecologically friendly RP‐HPLC methods based on the charged aerosol detector, Nove strategije u razvoju ekološki prihvatljivih RP‐HPLC metoda primenom detektora naelektrisanja u aerosolu",
volume = "71",
number = "5 suplement",
pages = "S24-S25",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4667"
}