Abstract: A validated simple and sensitive high performance liquid chromatographic (HPLC) method for the quantitative determination of nizatidine (NIZ) in human plasma and urine is reported. Reverse phase chromatographic separation of NIZ and salicylic acid (internal standard) was achieved on Diamonsil C18 column, using acetonitrile-0.05 mol/L K2HPO4-triethylamine (17:83:1, v/v/v, pH 6.5) as the mobile phase. Flow rate was 0.9 mL/min and the ultraviolet detector was set at a wavelength of 320 nm. The assay was linear over the range of 0.0117-6 mg/mL for plasma samples and 0.029-50 µg/mL for urine samples. The limit of quantification was 0.0117 μg/mL. The intra- and inter-day RSD values were lower than 5.12% and 8.03%, respectively, in plasma, and 6.2% and 6.9%, respectively, in urine. A single dose of 100 mg NIZ and multiple doses of 100 mg NIZ were administered to 10 healthy volunteers through intravenous infusions. The multiple dose regimens were administered every 8 h for 6 consecutive days. The pharmacokinetic parameters were obtained as following: for single-dose, Cmax (2.7±0.6) µg/mL, t1/2 (1.4±0.4) h, AUC0-12h (2.45±0.33) μg·h/mL, AUC_0-∞ (2.46±0.33) μg·h/mL, and the accumulated urine excretion rate in 12 h was 61.2%±9.46%; for multiple doses, Cmax (2.9±0.8) µg/mL, t1/2 (1.3±0.2) h, AUC0-12h (2.56±0.52) μg·h/mL, AUC_0-∞ (2.56±0.52) μg·h/mL, and the accumulated urine excretion rate in 12 h was 51.3%±9.42%. The statistical analysis of the pharmacokinetic parameters in males and females after single-dose and multiple-dose intravenous infusion of NIZ showed no differences. No drug accumulation after multiple-dose intravenous infusion of 100 mg NIZ was observed. The validated HPLC method was suitable for the pharmacokinetic study of NIZ.

Key words: Nizatidine, RP-HPLC, Pharmacokinetics