A quality-by-design eco-friendly UV-HPLC method for the determination of four drugs used to treat symptoms of common cold and COVID-19

Abstract

An optimization approach based on full factorial design was employed for developing an HPLC–UV method for simultaneous determination of a quaternary mixture used for the treatment of symptoms related to common cold and COVID-19. The quaternary mixture is composed of paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride. The developed technique is a green, fast and simple method that uses isocratic elution of mobile phase consisting of 20:5:75 (v/v) of ethanol: acetonitrile: 2.5 mM heptane-1-sulphonic acid sodium salt at pH 6.5 $$\pm$$ ± 0.02. The chromatographic separation was carried out using Hypersil BDS Cyano LC Column (250 × 4.6 mm, 5 μm) with 230 nm UV detection and 1.0 mL/min. flow rate. Avoiding the routine methodology and resorting to the modern technology—represented in the usage of experimental design—allows rapid determination of the four drugs using the optimum quantity of chemicals to avoid any waste of resources. The quaternary mixture was eluted in less than 9 min., where retention times of paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride were found to be 2.2, 3.8, 6.6 and 8.8 min., respectively. The calibration graphs of the four drugs were linear over concentration ranges of 50.0–500.0, 0.5–20.0, 0.5–20.0 and 0.5–100.0 µg/mL for paracetamol, levocetirizine dihydrochloride, phenylephrine hydrochloride and ambroxol hydrochloride, respectively with correlation coefficients higher than 0.999. The method is accurate with mean recoveries between 99.87 and 100.04%, precise, as %RSD for the intraday and interday precision were between 0.61 and 1.64% and very sensitive with limit of detections (LOD)’s between 29 and 147 ng/mL and limit of quantification (LOQ)’s between 95 and 485 ng/mL. The proposed method was successfully applied for the analysis of the four drugs either in raw materials or in prepared tablet with the least amount of chemicals within short time. It is also validated following International Conference on Harmonization Guidelines. The proposed method was found to be green according to the most common greenness assessment tools; NEMI, GAPI, Analytical Eco-Scale and AGREE methods. The advantages of the proposed method qualify it for routine analysis of the studied drugs either in single or co-formulated dosage form in quality control labs.

Hydro-organic mobile phase and factorial design application to attain green HPLC method for simultaneous assay of paracetamol and dantrolene sodium in combined capsules

“…Ethanol is the most trusted solvent from the viewpoint of environmental standard solvent guide [ 16 , 17 ]. Also, the usage of the experimental design allows the usage of optimum chemicals which decreases the waste and enhances the method greenness [ 18 ]. Herein, a validated, rapid, green and sensitive HPLC technique is presented for simultaneous determination of PAR and DAN in their combined capsules.…”

Efficacy and safety of paracetamol, phenylephrine, chlorpheniramine maleate and sodium citrate in Indian paediatric patients with common cold: an active post-marketing surveillance study

“…It is clinically represented by the symptoms of acute respiratory viral infections (ARVI) such as rhinorrhoea, nasal obstruction, nasal congestion, runny nose, and sneezing. [2][3][4] Adults typically get 2-3 upper respiratory tract infections (URTIs) per year, whereas children have 6-7 episodes per year, thus it is an important problem in paediatric practice. 5 Symptoms of the common cold in children typically reach peak intensity shortly after the onset of illness.…”

One-Step, Catalyst-Free Formation of Phenol from Benzoic Acid Using Water Microdroplets

“…Phenol and its substituted derivatives are found in many natural products. − Aromatic alcohol-containing scaffolds are widely used as synthetic intermediates in the perfume industry as well as in pharmaceuticals and textiles. − For example, phenol, itself, acts as an antiseptic and is used in aerosol form to treat sore throats . Similarly, the penicillin drug amoxicillin contains a phenol core, as do propofol, which is used to induce general anesthesia, and tolcapone, which is used to treat Parkinson’s disease. , Many other bioactive moleculessuch as the flavoring agent vanillic acid and the antioxidant gallic acidalso contain phenols .…”