OFAT versus DOE as two optimization protocols for the chromatographic analysis of some OTC pharmaceuticals carrying negative cardiovascular effects and administered by pregnant and breast-feeding females: Application to dose dependent effect

Abstract

<jats:title>Abstract</jats:title> <jats:p>A simple HPLC technique has been utilized for rapid and sensitive quantitative analysis of two mixtures of drugs that are used during pregnancy and lactation. Drugs of the first mixture are used to manage gastrointestinal tract illness that are common during early stages of pregnancy, while pharmaceutical agents of the second mixture are administered over the counter as galactagogues or to overcome postpartum depression. Mixture I includes famotidine (FMT), ranitidine (RNT), nizatidine (NZT), and pantoprazole (PNT), which were separated on a C18 column using a mobile phase composed of methanol: 0.02 M sodium dihydrogen phosphate (60:40, <jats:italic>v/v</jats:italic>) of pH 6.9, adopting UV detection at 240 nm at a flow rate of 1 mL/min. Mixture II on the other hand, consists of domperidone (DOM), metoclopramide (MET), and sulpiride (SUL). These drugs were eluted using the same column and flow rate as those in mixture I, using a mobile phase consisting of acetonitrile: 0.075 M sodium dihydrogen phosphate (30:70, <jats:italic>v/v</jats:italic>) of pH 6 adopting a detection wavelength 270 nm. Two optimization protocols were utilized to optimize the chromatographic separation conditions, namely one factor at a time (OFAT) and design of experiments (DOE) where face centered cube response surface experimental design was chosen for this investigation. Comparison of the results obtained from both protocols reveals the accordance between them.</jats:p> <jats:p>Full validation procedure under guidance of United States Pharmacopoeia (USP) was applied to the proposed methods which enabled their application to separate the drugs of both mixtures in spiked rat whole blood samples and <jats:italic>in vivo</jats:italic> analysis of rat heart blood.</jats:p>