@conference{
author = "Čarapić, Marija and Nikolić, Katarina and Smolinski, Adam and Agbaba, Danica",
year = "2018",
abstract = "Ziprasidon je novi atipični antipsihotik druge generacije, koji deluje kao
antagonista na serotoninskim i dopaminskim receptorima, i inhibira preuzimanje
norepinefrina. Glavni cilj hemometrijske studije je ispitivanje selektivnosti 20 reverznofaznih
(RP) stacionarnih faza u odnosu na ziprazidon i šest nečistoća ((I‐V) i
nepoznata). Velika strukturna sličnost ziprasidona i nečistoće II bila je ključni problem i
razdvajanje kritičnog para je bilo odlučujuće za odabir RP stacionarne faze.
Za analizu glavnih komponenti (PCA) korišćen je matematički program Soft
Independent Modeling of Class Analogy SIMCA P+ 12.0, a za analizu hijerarhijskog
grupisanja (HCA) korišćen je program MATLAB ver. 6.5.
Ispitivanje selektivnosti 20 RP stacionarnih faza je vršeno pri dobijenim
optimalnim eksperimentalnim uslovima (25 ºC; pH: 2,5; cTEA: 1% i cKH2PO4: 50mM) u
odnosu na ispitivana jedinjenja. Eksperimentalno dobijeni hromatografski parametri
(broj teoretskih platoa‐N, faktor simetrije pika ‐SF, rezolucija ‐Rs i faktor selektivnosti ‐
α između jedinjenja koja se blizu eluiraju) na 20 RP stacionarnih faza analizirani su
primenom PCA i HCA analiza.
Grafikoni rezultata i PCA koeficijenata variabli za PC1(osnovna komponeta 1) i
PC2 (osnovna komponeta 2) pokazuju glavne razlike između svih 20 RP‐kolona i glavne
sličnosti između hromatografskih parametara. Rs i α su odabrani kao najznačajniji
parametri za izbor stacionarne faze. Dobijeni dendogrami pokazali su tri glavne grupe
za stacionarne faze i četiri grupe za hromatografske parametre. Dendogrami RP kolona
i hromatografskih parametara su prikazani i obojenom mapom što je jednostavnija
metoda vizuelizacije.
Određene su RP stacionarne faze posebno selektivne za efikasno razdvajanje
ziprasidona i strukturno sličnih jedinjenja primenom PCA i HCA (grupa 1 PCA i grupa C
AHC):Waters Spherisorb® ODS1, Waters Spherisorb® ODS2 i Nucleosil® 100‐5 C18.
Dobijeni podaci su u skladu sa eksperimentalnim rezultatima. Odabrana je Waters
Spherisorb® ODS 1 kolona za HPLC metodu u odnosu na najbolju SF i faktor retencije
(k’)., Ziprasidone is a novel „atypical” or „second generation” antipsychotic drug
which acts primarily through serotonergic and dopaminergic receptor antagonism, and
as an inhibitor of the norepinephrine reuptake. The main aims of the presented
chemometric study was to test selectivity of the set of 20 Reversed‐phase (RP) ‐
columns towards ziprasidone and its six impurities ((I‐V) and one unknown).
Separation of structurally similar pair of ziprasidone/impurity II caused analytical
problems and was decisive for the selection of the suitable RP‐column.
The Principal Component Analysis (PCA) for column classification was done with
use of SIMCA P+ 12.0 program and Hierarchical Clustering Analysis (HCA) with use of
MATLAB ver. 6.5. with additional algorithms.
The obtained optimal chromatographic conditions (25C, pH 2,5, cTEA 1% and
cKH2PO4 50 mM) were used to test a set of 20 RP‐columns. Plate numbers (N),
symmetry factors (SF), resolution (Rs) and selectivity (α) of investigated compounds
were subjected to PCA and HCA analysis. Score plot and loading plots PC1 (principal
component 1) vs PC2 (principal component 2) visualize the main differences between
all 20 RP‐columns and main similarities between hromatographic parameters,
respectively. The Rs and α were selected as the most significant for the column
selection. The obtained dendrograms reveal three distinct clusters of RP‐columns and
four clusters of chromatographic parameters. The color map of data was used as a
simpler presentation of the dendrograms of RP‐columns and chromatographic
parameters.
The RP‐columns selective for the efficient separation of ziprasidone and its
structurally related compounds were defined by PCA and HCA (group 1 in PCA study
and same cluster C in HCA study) : Waters Spherisorb® ODS1, Waters Spherisorb®
ODS2 and Nucleosil® 100‐5 C18. The results were in accordance with experimentally
obtained results. Finally, the column Waters Spherisorb® ODS 1 was selected for the
HPLC method due to best SF and retention factor (k’).",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Primena metoda multivarijantnih analiza glavnih komponenti i hijerarhijskog grupisanja u ispitivanju razdvajanja jedinjenja ziprasidona tečnom hromatografijom, Modeling of liquid chromatography separation of ziprasidone compounds using multivariate methods of principal component and hierarchical clustering analysis",
volume = "68",
number = "3",
pages = "411-412",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4876"
}
