Distribution of Paroxetine in Postmortem Fluids and Tissues

Lewis RJ, Kemp PM, Johnson RD

FAA Office of Aerospace Medicine - Civil Aerospace Medical Institute

关键词: Forensic Toxicology;    Paroxetine;    GC/MS;    Postmortem Distribution;   

RP-ID  :  DOT/FAA/AM-15/11

美国|英语

来源: Federal Aviation Administration

【 摘 要 】

Paroxetine is a selective serotonin reuptake inhibitor that is a commonly prescribed drug for the treatment of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, premenstrual dysphoric disorder, and post-traumatic stress disorder. There are certain side effects associated with paroxetine use that could negatively affect a pilot's performance and become a factor in an aviation accident. Such side effects include nausea, drowsiness, insomnia, and dizziness. It has also been suggested that paroxetine use may increase suicidal behavior and suicidal ideation.When relying on postmortem specimens for interpretive value, a general understanding of drug distribution throughout postmortem fluids and tissues is important. Utilizing an n-butyl chloride liquid/liquid extraction followed by gas chromatograph/mass spectrometer (GC/MS) analysis with selected ion monitoring, our laboratory developed a method for the identification, characterization, and quantitation of paroxetine. The linear dynamic range was determined to be 3.13 - 1600 ng/mL in blood. Our laboratory then determined the postmortem concentrations of paroxetine in various postmortem tissues and fluids obtained from nine fatal aviation accident cases.The typical specimen types analyzed for each case included blood, urine, vitreous humor, liver, lung, kidney, spleen, muscle, brain, heart, and bile. Blood paroxetine concentrations obtained from these cases ranged from 0.019 to 0.865 µg/mL. The distribution of paroxetine, expressed as mean specimen/blood ratio, was: 1.67 ± 1.16 urine (n=4), 0.08 ± 0.04 vitreous humor (n=6), 5.77 ± 1.37 liver (n=8), 9.66 ± 2.58 lung (n=9), 1.44 ± 0.57 kidney (n=8), 3.80 ± 0.69 spleen (n=8), 0.15 ± 0.04 muscle (n=8), 4.27 ± 2.64 brain (n=7), and 1.05 ± 0.43 heart (n=8).The results from this study show that paroxetine is readily distributed to tissues and fluids in the body. The large standard deviations associated with the paroxetine distribution coefficients suggest that paroxetine likely can experience significant postmortem concentration changes.