A validated LC-MS/MS bioanalytical method for the pharmacokinetic interaction study of the effect of some co-administered COVID-19 protocol drugs on pholcodine containing antitussive mixture

Abstract

The symptoms of the viral infection COVID-19, which range from mild to severe, can include fever, coughing, sore throats, malaise, headaches, and a loss of taste or smell. Fever and cough are the most typical symptoms of COVID-19, and in more severe cases, it can make breathing difficult. Hence, in this in-vivo study, we studied the effect of the simultaneous co-administration of COVID-19 treatment drugs (azithromycin, dexamethasone, and hydroxychloroquine) on the pharmacokinetics of the antitussive drugs combination: pholcodine, pseudoephedrine and paracetamol in rats. For the simultaneous determination of pholcodine, pseudoephedrine, and paracetamol in rat plasma, a UPLC-MS/MS technique was developed and approved. a mobile phase made up of 0.15% aqueous formic acid: acetonitrile (20:80, v/v) was used using an Xterra C18 MS column (3.5 m, 4.6 × 50 mm). The detection procedure involved the employment of a multiple reaction monitoring mode utilizing triple-quadrupole tandem mass spectrometer. The concentration range for pholcodine, pseudoephedrine, and paracetamol was linear across 12–1000 ng/ml, 10–550 ng/ml, and 400–30000 ng/ mL, respectively. The results show that the coefficient of variation is satisfactory at quality control samples for all the mentioned drugs, confirming the accuracy and precision of the method. This approach was successfully implemented in a rat drug-drug pharmacokinetic interaction study to determine whether the co-administration of COVID-19 protocol medications would affect the bioavailability of pholcodine, pseudoephedrine and paracetamol. It was found that azithromycin, dexamethasone, and hydroxychloroquine co-administration significantly affect the bioavailability of these drugs, increasing their systemic exposure as a result and this could potentially lead to increasing adverse effects. Therefore, healthcare professionals should consider the potential drug-drug interaction when prescribing these medications to COVID-19 patients.