title: 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 methanol-induced 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 x 2.1 mm I.D., 5 microm) 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 microg/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 microg/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.
authors.affiliation: Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, The People's Republic of China.
authors.forename: Shudan
authors.initials: S
authors.lastname: Feng
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Zunjian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhang
authors.forename: Meihua
authors.initials: M
authors.lastname: Huang
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen