Influences of urinary pH on the pharmacokinetics of three amphetamine-type stimulants using a new high-performance liquid chromatographic method.
A simple and sensitive high-performance liquid chromatographic (HPLC) method after precolumn derivatization with 9,10-anthraquinone-2-sulfonyl chloride (ASC) has been developed and validated for the analysis of amphetamine-type stimulants (ATS) in biological samples. Based on this method, we investigated the impact of urinary pH on the pharmacokinetics of phenylpropanolamine (PPA), pseudoephedrine (PSE), and fenfluramine (FEN) in rats. The drugs were orally administrated to rats, which had been induced, by repeated oral doses of ammonium chloride or sodium bicarbonate, to excrete urine at lower or higher pH than the normal value, respectively. Results revealed that as the increase of urinary pH, the mean elimination half-life (t(1/2)), the mean residence time (MRT) and the area under the plasma concentration-time curve (AUC) of PPA, PSE, and FEN were greatly raised, while the total plasma clearance (CL/F) decreased considerably. These findings have important clinical implications.
Wang
Ling
L
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, People's Republic of China.
Feng
Fang
F
Wang
Xue Quan
XQ
Zhu
Lan
L
D000284:Administration, Oral; D000643:Ammonium Chloride / Q000008:administration & dosage; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005240:Feasibility Studies; D005277:Fenfluramine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D006863:Hydrogen-Ion Concentration; D008297:Male; D010665:Phenylpropanolamine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D054199:Pseudoephedrine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D017693:Sodium Bicarbonate / Q000008:administration & dosage; D014556:Urine / Q000737:chemistry*
D000697:Central Nervous System Stimulants; D000643:Ammonium Chloride; D005277:Fenfluramine; D010665:Phenylpropanolamine; D054199:Pseudoephedrine; D017693:Sodium Bicarbonate