Multi-criteria decision making approach for the optimization of atorvastatin and its impurities separation by micellar liquid chromatography

Abstract

In the current paper, multi-criteria decision making (MCDM) approach was applied to optimize micellar liquid chromatography (MLC) intended for the pharmaceutical analysis of atorvastatin and its impurities, trans-atorvastatin and desfluoro-atorvastatin. MLC is a reversedphase liquid chromatographic (RPLC) mode where the modification of mobile phase leads to the stationary phase modification. This results in the diverse interactions (hydrophobic, ionic and steric) significantly affecting retention and selectivity. For that reason double chained surfactant sodium dioctyl sulfosuccinate - AOT (Aerosol OT), with oxygen atoms in its tails, was used for the first time in such kind of separation. As the most efficient way to investigate a high number of factors, and simultaneously optimize defined antagonistic objectives (minimization of run time and maximization of atorvastatin and trans-atorvastatin resolution) MCDM approach was employed. Central composite design (CCD) with fractional factorial design, ± 0.5 star design and four replications in central point was used to define plan of experiments. Five responses selected during method development were optimized simultaneously using Derringer's desirability function. The predicted optimum was: 32 % acetonitrile, 2 % ethylene glycol, 66 % 6.4 mmol L-1 AOT in 20 mmol L-1 ammonium acetate, pH of the water phase 5.50 adjusted with acetic acid, flow rate 1.15 mL min-1 and column temperature of 10C.

U ovom radu, za optimizaciju metode micelarne tečne hromatografije (MLC) namenjene za farmaceutsku analizu atorvastatina i njegovih nečistoća, trans-atorvastatina i desfluoroatorvastatina primenjen je multikriterijumski pristup. MLC je oblik reverzno-fazne tečne hromatografije gde promene u mobilnoj fazi dovode i do modifikacije stacionarne faze. Ovo rezultuje različitim interakcijama (hidrofobnim, jonskim, sternim) sa značajnim uticajem na retenciju i selektivnost. Zbog toga je za separaciju odabran surfaktant koji sadrži dvostruki lanac i atom kiseonika, natrijum dioktil sulfosukcinat - AOT (Aerosol OT). Kao najefikasniji način za istraživanje velikog broja faktora i istovremenu optimizaciju suprotstavljenih ciljeva (minimizacija vremena trajanja razdvajanja i maksimizacija rezolucije između atorvastatina i trans-atorvastatina) primenjena je multikriterijumska optimizacija. Centralni kompozicioni dizajn (CCD) sa frakcionim faktorskim dizajnom, ± 0.5 zvezda dizajnom i četiri replikacije u centralnoj tački korišćen je za definisanje plana eksperimenta. Korišćenjem Derringer funkcije poželjnih odgovora, optimizirano je pet odgovora. Predviđeni optimalni uslovi bili su: 32 % acetonitrila, 2 % etilen-glikola, 66 % 6,4 mmol L-1 AOT u 20 mmol L-1 amonijum-acetatu, pH vodene faze 5,50 podešen sirćetnom kiselinom, protok 1,15 mL min-1 uz temperaturu kolone 10 C.