UPLC-MS/MS法研究雌性大鼠低剂量4-壬基酚暴露的代谢动力学

本文运用超高效液相色谱-串联质谱联用技术,建立了大鼠血清4-壬基酚的检测方法,以进行雌性大鼠低剂量4-壬基酚灌胃染毒后的代谢动力学研究。结果表明,血清样品基质不干扰4-壬基酚的测定,4-壬基酚在0.5~50.0 ng/mL的范围内线性关系良好(r=0.9950);检出限为0.09 ng/mL,定量限为0.30 ng/mL;方法的相对回收率为80.21%~104.23%;日内、日间相对标准偏差(RSD)均小于10%。代谢动力学研究表明,4-壬基酚在大鼠体内符合二房室模型,在0.04 h达到峰值浓度(C_max)24.34 ng/mL,外周室向中央室转运的速率(k₂₁=0.38/h)大于从中央室向外周室转运的速率(k₁₂=0.23/h),分布相半衰期(t_1/2α=1.12 h)小于消除相半衰期(t_1/2β=84.99 h),说明4-NP在体内呈现出吸收、分布速率高、清除速率低的代谢特点。

Metabolic Kinetics of Low Dose 4-Nonylphenol Exposure in Female Rats by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry

A method for the determination of 4-nonylphenol in rat serum was established by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)to study the metabolic kinetics of 4-nonylphenol in female rats after gavage administration of low dose of 4-nonylphenol. The results showed that the matrix effects did not interfere with the determination of 4-nonylphenol. The method showed good linear relationship with 0.5~50.0 ng/mL(r=0.9950),the limit of detection for 0.09 ng/mL,the limit of quantitation for 0.3 ng/mL. The relative recoveries were 80.21%~104.23%. The intra- and inter-day relative standard deviations(RSD)were less than 10%,respectively. Metabolic kinetics studies showed that 4-nonylphenol conformed to the two-compartment model in rats,the peak concentration(C_max)of 24.34 ng/mL at 0.04 h,and the rate of transport from the peripheral compartment to the central compartment(k₂₁=0.38/h)was greater than the rate of transport from the central compartment to the peripheral compartment(k₁₂=0.23/h),the distribution phase half-life(t1/2α=1.12 h)was smaller than the elimination phase half-life(t_1/2β=84.99 h). The results indicated that 4-nonylphenol had the characteristics of fast absorption,fast distribution and low clearance rate in vivo.