Abstract:
The current study was focused on establishing a novel ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method for the quantitative estimation of the co-formulated drugs; paracetamol (PAR), pseudoephedrine hydrochloride (PSD) and brompheniramine maleate (BRP) in human plasma to Egyptian volunteers. Additionally, the study aimed to recognize whether the co-administration of the target drugs to different ethnic population affects their pharmacokinetics. The drugs extraction involved liquid-liquid extraction technique with the aid of ethyl acetate. Reversed phase UPLC separation was accomplished on Agilent Zorbax SB C18 (50 mm � 2.1 mm, 1.8 ?m) column using acetonitrile: 0.1% formic acid (70: 30 v/v) as the mobile phase. Positive electrospray ionization and multiple reaction monitoring were employed. The short analysis time (1 min/sample) was promising as it has allowed the analysis of many human plasma samples per day. The developed method displayed linear ranges of 0.05�20.0 ?g/mL for PAR, 1.0�500.0 ng/mL for PSD and 0.1�50.0 ng/mL for BRP. A detailed validation of the developed method was performed in compliance with the FDA guidelines where all the validation parameters results were satisfactory. The UPLC-MS/MS method was utilized for studying the pharmacokinetics of the three drugs after the oral administration of their combined dosage form to Egyptian healthy volunteers. The pharmacokinetic study was accomplished after agreement of the ethics committee. The achieved pharmacokinetic results by the newly developed method were; Cmax (ng/mL) 8001.77, 127.76, 1.92, tmax (h) 0.75, 1.5, 4.0 and t� (h) 3.3, 4.65, 16.26 for PAR, PSD and BRP, respectively, these results were compared with those obtained from other reported clinical trials done on other races. It was clear that the pharmacokinetic parameters of PAR and PSD were not affected when the same dose was given to volunteers from different ethnic populations. Additionally, the co-administration of PSD and BRP with PAR has not altered the pharmacokinetics of PAR. The pharmacokinetics of PSD when it was co-administered with PAR and BRP was almost similar to that when it was co-administered with benorylate and chlorpheniramine, however, the Cmax of PSD was greatly affected when it was co-administered with caffeine, chlorpheniramine and cloperastine. � 2019 Elsevier B.V.
