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

Abstract

A novel method was developed for the simultaneous determination of guaifenesin (GUA) and ketorolac tromethamine (KET) enantiomers in plasma samples. Since GUA probably increases the absorption of coadministered drugs (e.g., KET), it would be extremely important to monitor KET plasma levels for the purpose of dose adjustment with a subsequent decrease in the side effects. Enantiomeric resolution was achieved on a polysaccharide-based chiral stationary phase, amylose-2, as a chiral selector under the normal phase (NP) mode and using ornidazole (ORN) as internal standard. This innovative method has the advantage of the ease and reliability of sample preparation for plasma samples. Sample clean-up was based on simply using methanol for protein precipitation followed by direct extraction of drug residues using ethanol. Both GUA and KET enantiomers were separated using an isocratic mobile phase composed of hexane/isopropanol/trifluoroacetic acid, 85:15:0.05 v/v/v. Peak area ratios were linear over the range 0.05-20 µg/mL for the four enantiomers S (+) GUA, R (-) GUA, R (+) KET, and S (-) KET. The method was fully validated according to the International Conference on Harmonization (ICH) guidelines in terms of system suitability, specificity, accuracy, precision, robustness, and solution stability. Finally, this procedure was innovative to apply the rationale of developing a chiral high-performance liquid chromatography (HPLC) procedure for the simultaneous quantitative analysis of drug isomers in clinical samples.

Simultaneous determination of guaifenesin enantiomers and ambroxol HCl using 50‐mm chiral column for a negligible environmental impact

“…LC techniques usually consume large volumes of high‐purity solvents used as extracting agents, cleaning agents, and mobile phases . Regarding the previous chiral HPLC methods for GUA, we have found that consumption of large amounts of hazardous solvents/run were followed . Reduction in waste volume through using 50‐mm‐length column along with using green solvents was our biggest challenge.…”

“…Utilizing Lux Cellulose‐1 as CSP (50 × 4.6 mm) for the first time in enantioseparation of GUA racemate with 1 mL min −1 flow rate allows the significant reduction in waste volume of solvents used. Figure shows the different volumes of solvents, per injection, used in published literature for elution of GUA enantiomers . A noticeable reduction in waste volume (about 3.5 mL) is observed, and only 1 mL of ethanol per injection, for achievement of complete GUA enantioseparation, is used following the proposed gradient profile.…”

“…A value between 0 and 1 is assigned for each category, resulting in an overall score between 0 (for the greenest) and 9 for each solvent . A quantitative assessment of the greenness of solvents used in this work is shown along with calculated values of the previous literature in Table . The table shows that the ethanol in the proposed method has a considerably small value for safety and minimum values for health and environmental hazard.…”

“…Since then, several CSPs have been reported for GUA enantiomers . Upon reviewing those methods, we found that GUA enantioseparation was achieved on different chiral columns (ranging in length from 100 to 250 mm) by using mobile phases consisting of different ratios of n‐heptane/ethanol, n‐heptane/isopropanol, n‐hexane/ethanol, and n‐hexane/isopropanol/trifluoroacetic acid . Aboul‐Enein et al have successfully developed a method for the separation of GUA enantiomers in pharmaceutical application with Ambroxol HCl (AMB) .…”

Electrochemical Sensor Based on Multiwalled Carbon Nanotube, Alizarine Red S and Chitosan for Simultaneous Determination of Oxomemazine Hydrochloride, Paracetamol and Guaifenesin

“…Guaifenesin (GU), [(R,S)‐3‐(2‐methoxyphenoxy)‐propane‐1,2‐diol], is a well‐known expectorant which is used orally in many cases such as acute respiratory tract infections, sinusitis, bronchitis and pharyngitis . GU was determined using different methods such as chromatographic , spectrophotometric and voltammetric methods .…”