2-溴-4-氟乙酰苯胺在雄性大鼠体内的毒物动力学行为

2-溴-4-氟乙酰苯胺(2-bromo-4-fluoroacetanilide,BFAA)是多种N-苯基酰胺类化合物合成的中间体,也是合成农药时的主要杂质.本研究建立了一种快速、特异的超高效液相色谱-串联质谱(UPLC-MS/MS)检测方法,用于测定大鼠血浆、组织、尿液和粪便中的2-溴-4-氟乙酰苯胺含量,以获得该化合...

Toxicokinetics of 2-bromo-4-fluoroacetanilide in male SD rat

2-Bromo-4-fluoroacetanilide (BFAA) is an intermediate in the synthesis of many N-phenylamides and an important impurity in the synthesis of pesticides. An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the rapid and specific determination of BFAA in rat plasma, tissue, urine and feces to obtain the toxicokinetic information of absorption, distribution and excretion of the compound. Plasma and different tissue samples of rats were obtained and processed by protein precipitation method after intragastric and intravenous administration with different doses of BFAA, and the validated UPLC-MS/MS method was used for detection. The absorption toxicokinetic parameters such as the peak time (t_max), the peak plasma drug concentration (C_max) and the area under the drug concentration-time curve (AUC_(0-t)), and bioavailability of BFAA were calculated. And the tissue distribution and excretion characteristics of urine and feces were investigated. The results of plasma toxicokinetic studies indicated that the drug was rapidly absorbed after intragastric administration, and the t_max value of the plasma concentration of BFAA was (0.2 ± 0.1), (0.4 ± 0.2) and (0.5 ± 0.3) h after given at 200, 500 and 1000 mg/kg, respectively. The C_max and AUC_(0-t) value were (32.4±5.0), (45.2±1.8), (38.5±3.2) mg/L and(121.2±40.9), (393.3±51.1), (321.9±38.0) (mg/L)·h, respectively. The bioavailability (F) of BFAA reached 34.1%-83.3%, and the plasma drug time curve had a double-peak phenomenon. It is speculated that there may be reabsorption or intestinal-hepatic circulation in animals. The results of tissue distribution studies showed that BFAA was widely distributed in the tissues and mainly distributed in small intestine, stomach and adipose tissue. In addition, a small fraction of BFAA was found in the brain and testis which indicated that the compound could cross the blood-brain barrier and testicular barrier. BFAA was eliminated in most tissues within 24 hours which indicated that there was no accumulation of the compound. The target distribution coefficient study suggested that BFAA has no obvious selectivity for tissues. Excretion through urine and feces mainly occurred within 0 to 48 hours, accounting for 93% and 92% of total excretion, respectively. The total excretion amount in urine and feces is (80.6 ± 29.8) μg, which only accounts for (0.03 ± 0.01) %, suggesting that the excretion in urine and feces is not the main elimination way of BFAA prototype compound in vivo.