LC-MS/MS Determination Of Pharmacokinetics Of4-Acetamidophenol In Monkey

Objective:To establish a LC-MS/MS method for the determination of4-Acetamidophenol in monkey plasma, and to investigate the pharmacokinetics of4-Acetamidophenol in monkey by using this method. Method:The blood samples were collected from6monkeys at different time points after administration of20mg/kg4-Acetamidophenol (p.o.). Methanol was used to precipitate the plasma albumen in the blood samples. Chromatographic separation was conducted by flowing the mobile phase through the Chromatographic Column (Phenmenex, Synergi4μ Polar-RP80A50x3.0mm). The concentration of4-Acetamidophenol in monkey plasma was determined by LC-ESI-MS/MS method with positive ion MRM scan type using Aceminophen-d4as an internal standard. Finally, pharmacokinetic parameters of4-Acetamidophenol were calculated. Results:Linearity of the method is good in the range from50ng/mL to50000ng/mL (r=0.9997). The lower limit of quantification (LLOQ) is50ng/mL. Following single oral administration of4-Acetamidophenol to monkeys at20mg/kg, the mean Cmax were observed at1hour postdose with8,900ng/mL for males and6,700ng/mL for females, respectively. The mean T1/2was1.3hours. The AUC0-∞was18,800h*ng/mL for males and12,100h*ng/mL for females, respectively. Conclusions:The method was proved to be accurate, sensitive, quick, simple, and reliable. It can be used for the determination of pharmacokinetics of4-Acetamidophenol in monkey.