@conference{
author = "Obradović, Darija and Savić, Jelena and Joksimović, Jovana and Marković, Bojan and Vujić, Zorica",
year = "2022",
abstract = "The serotonin receptor ligands, such as structurally related arylpiperazine and
benzothiazepine derivatives, are most commonly used in the treatment of schizophrenia,
depression, and manic disorders. (1). Due to emphasized lipophilicity, their retention can be
successfully defined under the reversed-phase (RP) chromatographic conditions. Using the
experimental design methodology (2), the retention of selected serotonin receptor ligands
(aripiprazole, ziprasidone, risperidone, olanzapine, quetiapine, mirtazapine) was tested on
RP stationary phases, in order to define differences in their retention mechanisms and
ensure the further optimization of separation conditions. The silica modified, C8 and
pentafluorophenylpropyl (PFP) columns were used as stationary phases, while the mobile
phase was a mixture of acetonitrile and ammonium acetate. The experimental plan was
defined according to the central composite design varying the following factors: ammonium
acetate concentration (15-25 mM), volume fraction of acetonitrile (40-50% v/v), and column
temperature (20-30°C). The differences between retention on C8 and PFP columns were
presented by using the radar plots and principal component analysis. The obtained
differences are especially visible in the case of ziprasidone, olanzapine, quetiapine and
mirtazapine, which may explain the occurrence of inversions in their elution order. On C8
phase the separation of structurally related arylpiperazine or benzothiazepine derivatives
was achieved, while the PFP phase showed more successful applicability in the separation of
all tested ligands. The slightly higher values of the selectivity parameter were obtained for
40% of acetonitrile in the mobile phase. In further optimization of the separation conditions,
the PFP bonded stationary phase can be successfully applied., Ligandi serotoninskih receptora kao što su strukturno srodni derivati arilpiperazina i
benzotiazepina, najčešće se koriste u terapiji oboljenja centralnog nervnog sistema, poput
šizofrenije, depresije, ili maničnog poremećaja (1). Zbog izraženih lipofilnih karakteristika,
njihovo retenciono ponašanje se može uspešno definisati u uslovima reverzno-fazne
(Reversed‐Phase, RP) tečne hromatografije. Primenom metodologije eksperimentalnog
dizajna (2), retencione karakteristike odabranih liganada serotoninskih receptora
(aripiprazol, ziprazidon, risperidon, olanzapin, kvetiapin, mirtazapin) su ispitane na RP
stacionarnim fazama, sa ciljem definisanja razlika u mehanizmima zadržavanja i daljoj
optimizaciji hromatografskih uslova razdvajanja. Kao stacionarne faze korišćene su C8 i
pentafluorofenilpropil (PFP) kolone, dok je mobilna faza bila smeša acetonitrila i amonijum-
acetata. Plan izvođenja eksperimenta je postavljen prema planu centralnog kompozitnog
dizajna variranjem sledećih hromatografskih faktora: koncentracije amonijum-acetata (15-
25 mM), zapreminskog udela acetonitrila (40-50% v/v) i temperature kolone (20-30°C).
Primenom linearne regresione analize, definisan je uticaj izabranih faktora na promenu
retencionog ponašanja (k) ispitivanih liganada. Korišćenjem radar grafika i primenom
analize glavnih komponenti predstavljene su razlike između mehanizama zadržavanja na C8
i PFP kolonama. Razlike su posebno vidljive u slučaju ziprazidona, olanzapina, kvetiapina i
mirtazapina čime se može objasniti inverzija u njihovom redosledu eluiranja. Uočeno je da
C8 stacionarna faza pogoduje razdvajanju strukturno srodnih arilpiperazina ili strukturno
srodnih derivata benzotiazepina, dok je PFP stacionarna faza pokazala uspešniju
primenljivost u razdvajanju svih ispitivanih liganada. Nešto veće vrednosti parametra
selektivnosti dobijene su na 40% udelu acetonitrila u mobilnoj fazi. U daljoj optimizaciji
hromatografskih uslova razdvajanja ispitivanih liganada, stacionarna faza sa vezanim PFP
grupama se može uspešno primeniti.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Optimization of reversed-phase conditions for separation of serotonin receptor ligands in liquid chromatography, Ptimizacija reverzno‐faznih uslova za razdvajanje liganada serotoninskih receptora u tečnoj hromatografiji",
volume = "72",
number = "4 suplement",
pages = "S548-S549",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4605"
}
