Određivanje podeonih koeficijenata i solvatohromnih parametara malih organskih molekula primenom tankoslojne hromatografije i hemometrije
Determination of partition coefficients and solvatochromic parameters of small organic molecules by thin-layer chromatography and chemometrics
Author
Andrić, Filip
Mentor
Milojković-Opsenica, Dušanka
Committee members
Tešić, Živoslav.
Đorđević, Dragana.

Metadata
Show full item recordAbstract
Cilj ove disertacije bio je razvoj metoda tankoslojne hromatografije za
određivanje podeonih koeficijenata, pre svega oktanol-voda (logKOW), zemljište-voda
(logKOC), vazduh-voda (logKAW) i solvatohromnih (A, B i S) parametara malih
organskih molekula na osnovu kojih se, primenom pristupa lineranih odnosa energije
solvatacije (LSER), mogu dalje proceniti: stepen aporpcije u gastrointestinalnom traktu
(% Abs), raspodela u sistemu krv-koža (logPskin), voda-koža (logKP, logKSC) i krvmoždana-barijera
(log BBB).
Za određivanje datih parametara izvorne metode su vremenski zahtevne,
podrazumevaju veliku količinu analita i imaju ograničeni radni opseg. Zbog toga su u
velikoj meri zamenjene različitim hromatografskim tehnikama, pre svega visokoefikasnom
tečnom hromatografijom (HPLC). Međutim, tankoslojna hromatografija ima
niz prednosti nad HPLC metodom. To je jednostavna, brza, jeftina metoda, koja koristi
male količine analita i reagenasa. Do sada nije sistematski ispitivana njena primena u
od...ređivanju pomenutih parametara.
U okviru ove disertacije primenjeni su različiti reverezno-fazni i normalno-fazni
hromatografski sistemi na skupu od 70 organskih jedinjenja malih molekulskih masa, u
kombinaciji sa različitim kalibracionim tehnikama: univarijantna regresija (OLS),
regresija glavnih komponenata (PCR), regresija metodom delimičnih najmanjih
kvadrata (PLS). Pri tome je izvršena selekcija hromatografskih sistema i definisanje
radnih opsega za svaki od proučavanih pariticionih koeficijenata te, tipova organskih
jedinjenja na koja se dati izbor hromatografskih uslova može primeniti. Razvijeni
postupci su okarakterisani parametrima preciznosti, tačnosti, prediktivne moći i ostalim
parametarima validacije modela
The aim of this thesis was the development of thin-layer chromatographic
methods for the determination of partition coefficients, primarily octanol-water
(logKow), soil-water (logKOC), air-to-water (logKAW ) and Abraham’s solvatochromic
parameters of small organic molecules which can be further used to estimate: the
gastrointestinal tract absorption (%Abs), the blood to skin distribution (logPskin), water
- skin (logKP, logKsc) and the blood to brain partition (logBBB).
Original methods used to determine the aforementioned parameters are time
consuming, involve a large amount of the analyte and have limited working range.
Therefore, they are, to a large extent, replaced by various chromatographic techniques,
especially high-performance liquid chromatography. However, thin-layer
chromatography has a number of advantages over HPLC method. It is simple, fast,
inexpensive method that uses small amounts of analytes and reagents. So far its
application in the determination of the parameters ...mentioned above has not been
systematically studied.
In the scope of this dissertation, several reversed-phase and normal-phase
chromatographic systems were applied on a set of 70 organic compounds of low
molecular weight in order to determine the partitioning as well as solvatochromic
parameters, in combination with a variety of calibration methods: univariate regression
(OLS), principal component regression (PCR), partial least squares regression (PLS).
For each of the studied pratitioning coefficients careful selection and definition of
chromatographic systems, operating conditions, working ranges and the types of organic
compounds on which the developed method could be applied have been done.
The developed methods were fruther characterized by the parameters of
precision, accuracy, predictive power, and other parameters of the model validation