Rapid simultaneous determination of paracetamol, amantadine hydrochloride, caffeine and chlorpheniramine maleate in human plasma by liquid chromatography/tandem mass spectrometry.

Shudan Feng, Yuan Tian, Zunjian Zhang, Jingjing Zhang, Meihua Huang, Yun Chen

Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing, The People's Republic of China.

Arzneimittel-Forschung 2009

filter terms:

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.

Citation

Shudan Feng, Yuan Tian, Zunjian Zhang, Jingjing Zhang, Meihua Huang, Yun Chen. Rapid simultaneous determination of paracetamol, amantadine hydrochloride, caffeine and chlorpheniramine maleate in human plasma by liquid chromatography/tandem mass spectrometry. Arzneimittel-Forschung. 2009;59(2):86-95