Rapid Simultaneous Determination of Paracetamol, Amantadine Hydrochloride, Caffeine and Chlorpheniramine Maleate in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry

Abstract

A rapid, simple and sensitive high performance liquid chromatography with positive ion electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was first developed and validated to simultaneously determine paracetamol (PAR, CAS 103-90-2), amantadine hydrochloride (ATH, CAS 665-66-7), caffeine (CAF, CAS 58-08-2) and chlorpheniramine maleate (CPM, CAS 113-92-8) in human plasma using tramadol hydrochloride (TMH, CAS 22204-88-2) as internal standard (IS). Following methanolinduced protein precipitation, the analytes were separated using a mobile phase comprised of methanol : water (0.5% formic acid) = 20 :80 (v/v) on a commercially available column (150 mm Ε 2.1 mm I.D., 5 μm) and analyzed by electrospray ionization tandem mass spectrometry in the selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 152.3 → 110.2 for PAR, 152.3 → 135.3 for ATH, 195.1 → 138.3 for CAF, 275.2 → 230.3 for CPM and 264.2 → 58.2 for TMH. The standard curves were linear (r² > 0.99) over the concentration range of 0.2–20 μg/mL for PAR, 20–2000 ng/mL for ATH and CAF, 0.1–10 ng/mL for CPM and had good accuracy and precision, respectively. The within- and between-batch precisions were less than 15% in terms of relative standard deviation (RSD). The lower limit of quantitation (LLOQ) were 0.2 μg/mL, 20 ng/mL, 20 ng/mL and 0.1 ng/mL for PAR, ATH, CAF and CPM, respectively. The described method has been successfully applied to study the pharmacokinetics of paracetamol-amantadine hydrochloride tablets in Chinese healthy male volunteers with great precision and sensitivity.

Key words

Amantadine hydrochloride - Caffeine - Chlorpheniramine maleate - HPLC-ESI-MS/MS - Paracetamol - Pharmacokinetics

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