Determination of depleted uranium, pyridostigmine bromide and its metabolite in plasma and urine following combined administration in rats

• Published in: Journal of pharmaceutical and biomedical analysis 2001-09, Vol.26 (2), p.281-289
• Main Authors: Abu-Qare, Aqel W, Abou-Donia, Mohamed B
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-nerve agent; Biological and medical sciences; Biological effects of radiation; Chemical and industrial products toxicology. Toxic occupational diseases; Cholinesterase Inhibitors - analysis; Cholinesterase Inhibitors - metabolism; Cholinesterase Inhibitors - toxicity; Chromatography, High Pressure Liquid - methods; Depleted uranium; Fundamental and applied biological sciences. Psychology; Gulf war veterans illness; Injections, Intradermal; Medical sciences; Muscle Weakness - chemically induced; N-Methyl-1,3-hydroxypyridinium bromide; Organometallic Compounds - analysis; Organometallic Compounds - toxicity; Organometallic Compounds - urine; Pyridostigmine bromide; Pyridostigmine Bromide - analysis; Pyridostigmine Bromide - metabolism; Pyridostigmine Bromide - toxicity; Radiocontamination; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Spectrophotometry - methods; Tissues, organs and organisms biophysics; Toxicology; Tremor - chemically induced; Uranium - metabolism; Various organic compounds
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/S0731-7085(01)00403-4

A simple and reliable method was developed for the quantification of depleted uranium, the anti nerve agent drug pyridostigmine bromide (PB;3-dimethylaminocarbonyloxy- N-methyl pyridinium bromide) and its metabolite N-methyl-3-hydroxypyridinium bromide in rat plasma and urine. The method involved using solid phase extraction and spectrophotometric determination of uranium, and high performance liquid chromatography (HPLC) with reversed phase C 18 column, and UV detection at 280 nm for PB and its metabolite. Uranium was derivatized using dibenzoylmethane (DBM) then the absorbance was measured at 405 nm. PB and its metabolite were separated using a gradient of 1–40% acetonitrile in 0.1% triflouroacetic acid water solution (pH 3.2) at a flow rate of 0.8 ml/min in a period of 14 min. Limits of detection were 2 ng/ml for uranium and 50 ng/ml for PB and its metabolite. Limits of quantitation were between 10 and 100 ng/ml for uranium and the other two analytes, respectively. Average percentage recovery of five spiked plasma samples were 83.7±8.6, 76.8±6.7, 79.1±7.1, and from urine 82.7±8.6, 79.3±9.5 and 78.0±6.2, for depleted uranium, PB and N-methyl-3-hydroxypyridinium bromide, respectively. The relationship between peak areas and concentration was linear for standards between 100 and 1000 ng/ml for all three analytes. This method was applied to analyze the above chemicals and metabolites following combined administration in rats.