Using dispersive liquid–liquid microextraction and liquid chromatography for determination of guaifenesin enantiomers in human urine

Abstract

A simple, rapid, and efficient method, dispersive liquid-liquid microextraction (DLLME) coupled with high-performance liquid chromatography-fluorescence detector, has been developed for the determination of guaifenesin (GUA) enantiomers in human urine samples after an oral dose administration of its syrup formulation. Urine samples were collected during the time intervals 0-2, 2-4, and 4-6 h and concentration and ratio of two enantiomers was determined. The ratio of R-(-) to S-(+) enantiomer concentrations in urine showed an increase with time, with R/S ratios of 0.66 at 2 h and 2.23 at 6 h. For microextraction process, a mixture of extraction solvent (dichloromethane, 100 μL) and dispersive solvent (THF, 1 mL) was rapidly injected into 5.0 mL diluted urine sample for the formation of cloudy solution and extraction of enantiomers into the fine droplets of CH(2)Cl(2). After optimization of HPLC enantioselective conditions, some important parameters, such as the kind and volume of extraction and dispersive solvents, extraction time, temperature, pH, and salt effect were optimized for dispersive liquid-liquid microextraction process. Under the optimum extraction condition, the method yields a linear calibration curve in the concentration range from 10 to 2000 ng/mL for target analytes. LOD was 3.00 ng/mL for both of the enantiomers.

Novel Stereoselective High‐Performance Liquid Chromatographic Method for Simultaneous Determination of Guaifenesin and Ketorolac Enantiomers in Human Plasma

“…In previous studies the separation of GUA enantiomers using polysaccharide columns was investigated. It was found that the enantiomers of GUA could be separated by normal phase HPLC using Chiralcel OD or Nucleocel Delta S columns (a tris(3,5dimethylphenyl‐carbamate) derivative of cellulose) with hexane/ethanol mobile phases. Thus, to avoid time‐consuming trial‐and‐error approaches, Lux cellulose‐1 column was first investigated because it has a similar chemical structure.…”

“…) has expectorant properties and is widely used in cough‐remedy formulations. It is used for short‐term relief of dry nonproductive cough and mucus in the breathing passages . GUA is thought to act as an expectorant by increasing the volume and reducing the viscosity of secretions in the trachea and bronchi.…”

“…Thus, it may increase the efficiency of the cough reflex and facilitate the removal of the secretions. GUA has R (–) and S (+) enantiomers, but it is widely used in racemic form as an expectorant in cough remedy formulations . While there have been no published reports about the antitussive pharmacological properties of the individual enantiomers of GUA, it has recently been speculated that perhaps one enantiomer may have greater physiological activity or fewer undesired side effects than the other enantiomer.…”

“…Previous reports indicated that GUA enantiomers could be well separated by normal phase HPLC using polysaccharide‐based stationary phases, namely, tris (3,5‐dimethylphenyl carbamate) derivative of cellulose and tris (3,5‐dimethylphenyl carbamate) derivative of amylose . However, these methods suffered from some major drawbacks, such as complicated operating systems, the need of special instrumentation requirements, and tedious laboratory experimentation, making the procedure time‐consuming and with more expected errors. Moreover, with the exception of Hatami et al, all reported methods were just qualitative and did not include any validation or quantitative studies.…”

Chemistry of drug interactions: Characterization of charge-transfer complexes of Guaifenesin with various acceptors using spectroscopic and thermal methods

“…1), is a constituent of guaiac resin from the wood of Guajacum officinale [1]. It is a widely used expectorant drug, and usually is taken orally to assist the bringing up of phlegm from the airway in acute respiratory tract infections and can be used for treatment sinusitis, pharyngitis, and bronchitis [2][3][4][5][6]. It is termed an expectorant since it is believed to alleviate cough discomfort by increasing sputum volume and decreasing its viscosity (hydration hypothesis), thereby promoting effective cough.…”