Ionophore-Based Potentiometric Sensors for the Flow-Injection Determination of Promethazine Hydrochloride in Pharmaceutical Formulations and Human Urine

Ahmed Khudhair Hassan,Marina Mokhtar,Rohana Adnan,Suham Towfiq Ameen,Bahruddin Saad,Afidah Abdul Rahim,Sulaiman Ab Ghani,Suad Mustafa Al-Araji,Norariza Ahmad

doi:10.3390/s110101028

Abstract

Plasticised poly(vinyl chloride)-based membranes containing the ionophores (α-, β- and γ-cyclodextrins (CD), dibenzo-18-crown-6 (DB18C6) and dibenzo-30-crown-10 (DB30C10) were evaluated for their potentiometric response towards promethazine (PM) in a flow injection analysis (FIA) set-up. Good responses were obtained when β- and γ-CDs, and DB30C10 were used. The performance characteristics were further improved when tetrakis(4-chlorophenyl) borate (KTPB) was added to the membrane. The sensor based on β-CD, bis(2-ethylhexyl) adipate (BEHA) and KTPB exhibited the best performance among the eighteen sensor compositions that were tested. The response was linear from 1 × 10−5 to 1 × 10−2 M, slope was 61.3 mV decade−1, the pH independent region ranged from 4.5 to 7.0, a limit of detection of 5.3 × 10−6 M was possible and a lifetime of more than a month was observed when used in the FIA system. Other plasticisers such as dioctyl phenylphosphonate and tributyl phosphate do not show significant improvements in the quality of the sensors. The promising sensors were further tested for the effects of foreign ions (Li+, Na+, K+, Mg2+, Ca2+, Co2+, Cu2+, Cr3+, Fe3+, glucose, fructose). FIA conditions (e.g., effects of flow rate, injection volume, pH of the carrier stream) were also studied when the best sensor was used (based on β-CD). The sensor was applied to the determination of PM in four pharmaceutical preparations and human urine that were spiked with different levels of PM. Good agreement between the sensor and the manufacturer’s claimed values (for pharmaceutical preparations) was obtained, while mean recoveries of 98.6% were obtained for spiked urine samples. The molecular recognition features of the sensors as revealed by molecular modelling were rationalised by the nature of the interactions and complexation energies between the host and guest molecules.

Highlights

Promethazine hydrochloride (PM) [(RS)-N,N-dimethyl-1-(10H-phenothiazine-10-yl)propan-2-amine hydrochloride] is a phenothiazine derivative (Figure 1)
This study aims in developing a simple, rapid and selective PM sensor that can be used for the determination of PM in real samples
An important property of CDs is their ability to form inclusion complexes with a large number of organic and inorganic compounds―a property that has been exploited in pharmaceutical formulations of certain drugs [36]

Summary

Introduction

Promethazine hydrochloride (PM) [(RS)-N,N-dimethyl-1-(10H-phenothiazine-10-yl)propan-2-amine hydrochloride] is a phenothiazine derivative (Figure 1). It is a first generation H1 receptor antagonist, antihistamine and antiemetic medication and can have strong sedative effects [1,2,3]. Have been used for the assay of PM in pharmaceutical formulations. Most of these methods are complicated, time consuming and require expensive instrumentation. The oxidised form of PM is unstable which requires a rapid and fully automated reagent handling technique [10,11,12]. There is a need for simpler, low-cost, sensitive and rapid alternative methods for the determination of PM in real samples

Objectives

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Conclusion