3-Quinuclidinyl benzilate (agent BZ) toxicokinetics in rats.

3-Quinuclidinyl benzilate (BZ) ranks among incapacitating military warfare agents. It acts as a competitive inhibitor on muscarinic receptors leading to non-lethal mental impairment. The present study aimed to investigate toxicokinetics of BZ in rats. Moreover, BZ can be exploited to produce a pharmacological model of Alzheimer's disease; thus, this paper focuses mainly on the BZ distribution to the brain. Wistar rats were administered i.p. with BZ (2 and 10 mg/kg). The BZ concentration was determined using LC-MS/MS in plasma, urine, bile, brain, kidney and liver. The sample preparation was based on a solid phase extraction (liquids) or protein precipitation (organ homogenates). The plasma concentration peaked at 3 min (204.5 ± 55.4 and 2185.5 ± 465.4 ng/ml). The maximal concentration in the brain was reached several minutes later. Plasma elimination half-life was 67.9 ± 3.4 in the 2 mg/kg group and 96.6 ± 27.9 in the 10 mg/kg group. BZ concentrations remained steady in the brain, with slow elimination (t1/2 506.9 ± 359.5 min). Agent BZ is excreted mainly via the urine. Steady BZ concentration in the brain could explain the previously published duration of the significant impairment in passive avoidance tasks in rats after an injection of BZ.

Determination of 3-quinuclidinyl benzilate (QNB) and its major metabolites in urine by isotope dilution gas chromatography/mass spectrometry.

In response to the scheduled destruction of U.S. military stockpiles of the hallucinogenic agent 3-quinuclidinyl benzilate (QNB), a specific confirmatory test for human exposure to QNB was developed. The amount of the parent compound in the urine as well as the two major metabolites, 3-quinuclidinol (Q) and benzilic acid (BA), was determined because the relationship between QNB dose and levels of QNB and its metabolites in human urine is not known. QNB was determined in urine samples spiked at a target level of 0.5 ng/mL, and the metabolites BA and Q were determined at a target level of 5 ng/mL. The method uses solid-phase extraction to isolate each analyte from the urine and isotope dilution gas chromatography/mass spectrometry for quantitation. Each analyte is converted to its trimethylsilyl derivative for analysis. The analytical method was tested on eight different urine samples spiked with known amounts of the analytes near the target levels, at 10 times the target levels, and blank (unspiked) urine samples. The variabilities in the method are for the most part evenly distributed between three imprecision categories: GC/MS measurement, sample preparation, and the urine samples. The total imprecision (1 standard deviation) of a single measurement is about 15% of the value for each analyte.