Postmortem Fluid and Tissue Concentrations of THC, 11-OH-THC and THC-COOH.

Marijuana is the most commonly abused illicit drug worldwide. Marijuana is used for its euphoric and relaxing properties. However, marijuana use has been shown to result in impaired memory, cognitive skills and psychomotor function. The Federal Aviation Administration's Civil Aerospace Medical Institute conducts toxicological analysis on aviation fatalities. Due to severe trauma associated with aviation accidents, blood is not always available; therefore, the laboratory must rely on specimens other than blood for toxicological analysis in ~30-40% of cases. However, the postmortem distribution of cannabinoids has not been well characterized. The purpose of this research is to evaluate the distribution of Δ9-tetrahydrocannabinol (THC), and its metabolites, 11-hydroxy-tetrahydrocannabinol (11-OH-THC) and THC-COOH, in postmortem fluid and tissue specimens from 11 fatal aviation accident cases (2014-2015) previously found positive for cannabinoids. Specimens evaluated, when available, included: blood, urine, vitreous humor, liver, lung, kidney, spleen, muscle, brain, heart and bile. We developed and validated (following SWGTOX guidelines) a sensitive and robust method using solid-phase extraction and liquid chromatography-tandem mass spectrometry to identify and quantify THC, 11-OH-THC and THC-COOH in postmortem fluids and tissues. The method readily identified and quantified these cannabinoids in postmortem fluids and tissues below 1 ng/mL. Qualitative cannabinoid results within each case were comparable between blood and non-blood specimens. However, there was no consistent distribution of the cannabinoids between blood and any other fluids or tissues. Therefore, while quantitative interpretation of non-blood postmortem fluid and tissues samples is not prudent, a majority of the non-blood specimens tested could be suitable alternative/supplemental choices for qualitative cannabinoid detection.

Paroxetine in Postmortem Fluids and Tissues from Nine Aviation Accident Victims.

Paroxetine is a selective serotonin reuptake inhibitor commonly prescribed for the treatment of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder and post-traumatic stress disorder. While the use of paroxetine is considered relatively safe, negative side effects, including nausea, drowsiness, insomnia and dizziness, can adversely affect a pilot's ability to safely operate an aircraft. The use of paroxetine may increase suicidal behavior and suicidal ideation. When relying on postmortem specimens for toxicological evaluation, a general understanding of drug distribution throughout postmortem specimens is important. This laboratory has determined the distribution of paroxetine in postmortem tissues and fluids from nine aviation accident fatalities. Specimens were processed using an n-butyl chloride liquid/liquid extraction followed by gas chromatographic/mass spectrometeric analysis. 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 large standard deviations associated with the paroxetine distribution coefficients suggest that paroxetine can experience significant postmortem concentration changes.

Analysis of zolpidem in postmortem fluids and tissues using ultra-performance liquid chromatography-mass spectrometry.

Zolpidem is a nonbenzodiazepine sedative hypnotic drug used for the short-term treatment of insomnia. While quite effective in producing sedation, zolpidem has potentially hazardous side effects when put in the context of complex tasks. Therefore, to more fully understand the postmortem concentrations of zolpidem, our laboratory has developed a sensitive method for the quantitation of zolpidem in biological specimens. Additionally, we have evaluated the distribution of zolpidem in various postmortem tissues and fluids from 10 aviation fatalities. This method incorporated a modified acetonitrile 'crash and shoot' extraction and a Waters Xevo TQ-S with an Acquity ultra-performance liquid chromatograph. The linear dynamic range was 0.4-800 ng/mL. The extraction efficiencies ranged from 78 to 87%, depending on the concentration. Postmortem blood zolpidem concentrations in these 10 cases ranged from 7.6 to 76.5 ng/mL. The highest concentrations of zolpidem present in each victim were found in the liver, spleen, lung and kidney tissues. Distribution coefficients for zolpidem were determined for each of the specimen types analyzed. These coefficients are expressed relative to the blood concentration in each case. This method proved to be simple, accurate and robust for the identification and quantitation of zolpidem in postmortem fluids and tissues.

False carbamazepine positives due to 10,11-dihydro-10-hydroxycarbamazepine breakdown in the GC-MS injector port.

During the investigation of aviation accidents, postmortem specimens from accident victims are submitted to the Federal Aviation Administration's Civil Aerospace Medical Institute (CAMI) for toxicological analysis. A case recently received by CAMI screened positive for the anticonvulsant medication carbamazepine (CBZ; Tegretol(®)) by gas chromatography-mass spectrometry (GC-MS). The CBZ found during this routine screening procedure was subsequently confirmed using a CBZ-specific GC-MS procedure. It was later discovered that the accident victim had been prescribed oxcarbazepine (OXCBZ; Trileptal(®)). OXCBZ is structurally similar to CBZ and is metabolized by cytosolic enzymes in the liver to an active metabolite, 10,11-dihydro-10-hydroxycarbamazepine (DiCBZ). It was determined that the CBZ initially found in this case was present due to the thermal breakdown of DiCBZ in the GC-MS injector port. In the current study, this conversion was investigated and the percentage of CBZ formed at various injector port temperatures was determined. Additionally, these three compounds were quantified in nine fluid and tissue specimens from the case in question. Liquid chromatography-mass spectrometry was also incorporated to further demonstrate the absence/presence of CBZ in these samples.

A new equation for calculating the maximum wait time for pilots who use an impairing medication.

INTRODUCTION: Pilots who use an impairing medication to treat a medical condition are required to wait an appropriate amount of time after completing the treatment before returning to duty. However, toxicology findings from fatal aviation accidents indicate not all pilots wait a sufficient period of time. Methods used today do not take into consideration the time required for the drug to reach subtherapeutic concentrations. METHODS: An equation was developed based on the therapeutic range and the maximum expected half-life of the medication to objectively calculate a safe return-to-duty time for pilots. The new equation assumes the treating physician will not dose the patient beyond the upper therapeutic range of the medication and the person taking the medication has the maximum half-life reported in the literature. The equation N ln(0.5*Cmin/Cmax)/ln(0.5) was developed to determine the number of half-lives (n) required to reach one-half of Cmin, where Cmin = lower therapeutic concentration and Cmax = upper therapeutic concentration. Anonymous subjects were recruited under an approved IRB protocol. Blood and plasma were collected at approximately Cmax (2-3 h) and again after waiting approximately another 5 h. Toxicological analysis was performed on the specimens collected. RESULTS: One subject taking a 25-mg dose had a 0.033 ug x ml(-1) blood concentration after waiting 8 h, well above the 0.025 ug x ml(-1) reported as impairing concentration. The new equation estimated a mean wait time for the 18 medications composed of 4 half-lives. DISCUSSION: The new CAMI equation takes into consideration safety without grossly over estimating pilot wait times.

Analysis of sertraline in postmortem fluids and tissues in 11 aviation accident victims.

Sertraline (Zoloft) 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. Although the use of sertraline is relatively safe, certain side effects may negatively affect a pilot's performance and become a factor in an aviation accident. The authors' laboratory investigated the distribution of sertraline and its primary metabolite, desmethylsertraline, in various postmortem tissues and fluids obtained from 11 fatal aviation accident cases between 2001 and 2004. Eleven specimen types were analyzed for each case, including blood, urine, vitreous humor, liver, lung, kidney, spleen, muscle, brain, heart and bile. Human specimens were processed utilizing solid-phase extraction, followed by characterization and quantitation employing gas chromatography-mass spectrometry. Whole blood sertraline concentrations obtained from these 11 cases ranged from 0.005 to 0.392 µg/mL. The distribution coefficients of sertraline, expressed as specimen/blood ratio, were as follows: urine, 0.47 ± 0.39 (n = 6); vitreous humor, 0.02 ± 0.01 (n = 4); liver, 74 ± 59 (n = 11); lung, 67 ± 45 (n = 11); kidney, 7.4 ± 5 (n = 11); spleen, 46 ± 45 (n = 10); muscle, 2.1 ± 1.3 (n = 8); brain, 22 ± 14 (n = 10); heart, 9 ± 7 (n = 11); and bile, 36 ± 26 (n = 8). Postmortem distribution coefficients obtained for sertraline had coefficients of variation ranging from 47-99%. This study suggests that sertraline likely undergoes significant postmortem redistribution.

Postmortem ethanol in the setting of ethanol-containing automotive fuel.

The pilot of a light aircraft that crashed after a loss of power was found to have ethanol in the vitreous and the blood, but almost none in the urine. The globes of the eyes were intact, and the body was refrigerated after recovery until the autopsy was performed the following morning. The pilot was described as a "nondrinker," and additional specialized toxicology testing results were inconsistent with ethanol ingestion. The pilot's body was extensively exposed to fuel during the prolonged extraction. Investigation determined that the aircraft had been fueled with gasoline that contained 10% ethanol. Although exposure to automotive fuel has not been previously described as a source of ethanol in postmortem specimens, it may represent a source for the ethanol detected during postmortem toxicology testing in this case, and this finding may be relevant to other cases with similar exposure.

Increased cannabinoids concentrations found in specimens from fatal aviation accidents between 1997 and 2006.

The National Institute on Drug Abuse (NIDA) and the Office of National Drug Control Policy (ONDCP) reported a 1.5-fold increase in the delta-9-tetrahydrocannabinol (THC) content of street cannabis seizures from 1997 to 2001 versus 2002 to 2006. This study was conducted to compare the changes, over those years, in blood and urine cannabinoid concentrations with the potency of THC reported in the cannabis plant. Cannabinoids were screened using radioimmunoassay (RIA) for blood and fluorescence polarization immunoassay (FPIA) for urine and confirmed using GC/MS. A total of 95 individuals were found to be using cannabis from a total number of 2769 (3.4%) individuals tested over the period 1997 through 2006. Other impairing drugs were found in 38% of the cannabinoids-positive individuals. The mean concentration of THC in blood for 1997-2001 was 2.7 ng/mL; for 2002-2006, it was 7.2 ng/mL, a 2.7-fold increase in the mean THC concentration of specimens from aviation fatalities, compared to a 1.5-fold increase in cannabis potency reported by the NIDA and ONDCP. The mean age for cannabis users was 40 years (range 18-72) for aviation fatalities. For all blood and urine specimens testing negative for cannabinoids from aviation fatalities, the mean age of the individuals was 50 years (range 14-92). More than half of the fatalities tested were 50 years or older, whereas, 80% of the positive cannabis users were under 50. As indicated by these findings, members of the transportation industry, government regulators, and the general public should be made aware of the increased potential for impairment from the use of high-potency cannabis currently available and being used.

The postmortem distribution of vardenafil (Levitra) in an aviation accident victim with an unusually high blood concentration.

Vardenafil (Levitra) is one of the most widely prescribed treatments for erectile dysfunction. This report presents a rapid and reliable method for the identification and quantification of vardenafil in postmortem fluids and tissues, applies this method to a postmortem case, and describes the distribution of vardenafil in various fluids and tissues. This procedure utilizes sildenafil-d8, which is structurally closely related to vardenafil, as an internal standard for more accurate and reliable quantitation. The method incorporates solid-phase extraction and liquid chromatography-tandem mass spectrometry (MS) and MS-MS-MS utilizing an atmospheric pressure chemical ionization ion trap MS in the positive chemical ionization mode. Solid-phase extraction proved to be exceptionally efficient providing recoveries that ranged from 94% to 97%. The limit of detection for vardenafil was determined to be 0.19 ng/mL. The linear dynamic range for this compound was 0.39-200 ng/mL. This method was successfully applied to postmortem fluid and tissue specimens obtained from an aviation accident victim. The distribution of vardenafil in various fluids and tissues and the unusually high concentration of vardenafil in the victim's blood are examined.

The distribution of fluoxetine in human fluids and tissues.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that was introduced in 1986. Certain side effects of this medication-drowsiness, dizziness, abnormal vision, diarrhea, and headache-could affect pilot performance and become a factor in an aviation accident. Our laboratory has determined the distribution of fluoxetine and its desmethyl metabolite, norfluoxetine, in various postmortem tissues and fluids from 10 fatal aviation accident cases. When available, 11 specimen types were analyzed for each case, including blood, urine, vitreous humor, bile, liver, kidney, skeletal muscle, lung, spleen, heart muscle, and brain. Blood fluoxetine concentrations in these 10 cases ranged from 21 to 1480 ng/mL. The distribution coefficients for both fluoxetine and norfluoxetine, expressed as specimen/blood ratios, were determined. The distribution coefficients for fluoxetine were determined to be 0.9 +/- 0.4 for urine, 0.10 +/- 0.03 for vitreous humor, 9 +/- 1 for bile, 38 +/- 10 for liver, 60 +/- 17 for lung, 9 +/- 3 for kidney, 20 +/- 5 for spleen, 2.2 +/- 0.3 for muscle, 15 +/- 3 for brain, and 10 +/- 2 for heart. To our knowledge, this is the first report presenting the distribution of fluoxetine in humans at therapeutic concentrations.

Bone morphogenetic proteins and their receptor signaling in prostate cancer.

Bone morphogenetic proteins (BMPs) belong to the TGF-Beta superfamily and are vital bone inductive factors. BMPs also play important roles during embryonic development and the postnatal homeostasis of various organs and tissues, by controlling cellular differentiation, proliferation and apoptosis. Prostate cancer is the most common cancer in men in Western countries, with a high incidence of bone metastasis. Once bony metastasis developed, the condition is incurable, and contributes significant disease specific morbidity and mortality. However, the mechanisms underlying the development of bone metastasis remain unclear. BMPs have been implicated in the development of both primary and secondary tumors, particularly skeletal metastasis. Aberrations in BMPs signaling have also been identified in various neoplasms. Recently studies have also suggested a pivotal role in bone metastasis for Noggin, which is a BMP antagonist. In this review, we discuss the current knowledge of BMPs signaling, abnormalities which have been identified and their involvement in tumour progression, and particularly in the development of bone metastasis in prostate cancer.

Aircraft-assisted pilot suicides in the United States, 1993-2002.

Our laboratory was interested in epidemiological and toxicological findings from aircraft-assisted pilot suicides. Between 1993-2002 there were 3,648 fatal aviation accidents. The NTSB determined that 16 were aircraft-assisted suicides; 15 from intentional crashing of an aircraft and 1 from exiting the aircraft while in-flight. All pilots involved in these aircraft-assisted suicides were male, with a median age of 40 years. Seven of the 14 pilots for which specimens were available were positive for disqualifying substances. Based on the few cases conclusively attributed to suicide, death by the intentional crashing of an aircraft appears to be an infrequent and uncommon event.

Pilot medical history and medications found in post mortem specimens from aviation accidents.

INTRODUCTION: Federal Aviation Administration (FAA) regulations require pilots to report all medications and medical conditions for review and consideration as to the overall suitability of the pilot for flight activities. METHODS: Specimens were collected by local pathologists from aviation accidents and sent to the Bioaeronautical Sciences Research Laboratory for analysis. The results of such tests were entered into the Forensic Case Management System. This database was searched to identify all pilots found positive for medications used to treat cardiovascular, psychological, or neurological conditions over the period January 1, 1993, through December 31, 2003. RESULTS: Toxicological evaluations were performed on 4143 pilots. Psychotropic drugs were found in 223 pilots. Cardiovascular medications were found in 149 pilots. Neurological medications were found in 15 pilots. Pilots reported psychological conditions in 14 of the 223 pilots found positive for psychotropic drugs. Only 1 of the 14 pilots reporting a psychological condition to the FAA reported the psychotropic medication found after the accident. Cardiovascular disease was reported by 69 of the pilots found with cardiovascular drugs in their system. Cardiovascular medications found in the pilots were reported by 29 of the 69 pilots reporting a cardiovascular condition. Only 1 of the 15 pilots reported having a neurological condition to the FAA; none of the pilots found with neurological medications reported the medication. CONCLUSIONS: Toxicology successfully identified 93% of the medications reported by the pilots. Pilots involved in fatal accidents taking psychotropic or neurological medications rarely reported the medication or their underlying medical condition to the FAA.

Quantitative determination of sildenafil (Viagra) and its metabolite (UK-103,320) in fluid and tissue specimens obtained from six aviation fatalities.

During the investigation of aviation accidents, postmortem samples from victims are submitted to the Federal Aviation Administration's Civil Aerospace Medical Institute for toxicological analysis. This report presents a rapid and reliable method for the identification and quantitation of sildenafil (Viagra) and its active metabolite, UK-103,320. This procedure utilizes sildenafil-d(8) as an internal standard for more accurate and reliable quantitation. The quantitation of sildenafil and UK-103,320 in postmortem fluid and tissue specimens obtained from victims from six separate aviation fatalities is described. The method incorporates solid-phase extraction and liquid chromatography-tandem mass spectrometry (LC-MS-MS) and MS-MS-MS utilizing an atmospheric pressure chemical ionization ion trap MS in the positive chemical ionization mode. Solid-phase extraction provided an efficient sample extraction yielding recoveries ranging from 79 to 88%. The limits of detection for sildenafil and UK-103,320 were 0.39 and 0.19 ng/mL, respectively. The linear dynamic range for both compounds was 0.78-800 ng/mL. The current method proved to be simple, accurate, and robust for the identification and quantitation of sildenafil and UK-103,320 in postmortem fluids and tissues.

Quantitation of atenolol, metoprolol, and propranolol in postmortem human fluid and tissue specimens via LC/APCI-MS.

Hypertension is a growing medical concern in the United States. With the number of Americans suffering from hypertension increasing, the use of antihypertensives such as beta-blockers is increasing as well. In fact, three beta-blockers - atenolol, metoprolol and propranolol - were among the 200 most prescribed medications in the United States in 2003. Pilots that successfully manage their hypertension can remain certified to fly. The Federal Aviation Administration currently designates approximately 8% of active pilots as "hypertensive with medication". The Civil Aerospace Medical Institute (CAMI) performs toxicological evaluation on victims of fatal aviation accidents. At CAMI beta-blockers are analyzed using gas chromatography with mass spectrometric detection. We have, however, recently developed a liquid chromatography with mass spectrometric detection (LC/MS) method for the simultaneous quantitation of three commonly prescribed beta-blockers, atenolol, metoprolol and propranolol. One advantage of our LC/MS method is the specificity provided by an ion trap MS. Utilizing an ion trap MS, we were able to conduct MS/MS and MS/MS/MS on each analyte. This method also eliminates the time-consuming and costly derivitization step necessary during GC/MS analysis. Additionally, by utilizing this novel method, any concerns about beta-blocker metabolite and/or sample matrix interference are eliminated. The limits of detection for this method ranged from 0.39 to 0.78 ng/mL and the linear dynamic range was generally 1.6-3200 ng/mL. The extraction efficiencies for each analyte ranged from 58% to 82%. This method was successfully applied to postmortem fluid and tissue specimens obtained from victims of three separate aviation accidents.

Gas chromatographic-mass spectrometric differentiation of atenolol, metoprolol, propranolol, and an interfering metabolite product of metoprolol.

Over a 10-year period, 1993-2002, Federal Aviation Administration identified 50 pilot fatalities involving atenolol, metoprolol, and propranolol, which is consistent with the fact that these drugs have been in the lists of the top 200 drugs prescribed in the U.S. In a few of the 50 pilot fatality cases, initial analysis suggested the presence of atenolol and metoprolol. However, there was no medical history with these cases supporting the use of both drugs. Therefore, atenolol, metoprolol, and/or propranolol, with their possible metabolite(s), were re-extracted from the selected case specimens, derivatized with pentafluoropropionic anhydride (PFPA), and analyzed by gas chromatography-mass spectrometry (GC-MS). The MS spectra of these three antihypertensives and a metoprolol metabolite are nearly identical. All of the PFPA derivatives had baseline GC separation, with the exception of a metoprolol metabolite product, which co-eluted with atenolol. There were four primary mass fragments (m/z 408, 366, 202, and 176) found with all of the PFPA-beta-blockers and with the interfering metabolite product. However, atenolol has three unique fragments (m/z 244, 172, and 132), metoprolol has two unique fragments (m/z 559 and 107), propranolol has four unique fragments (m/z 551, 183, 144, and 127), and the metoprolol metabolite product has two unique fragments (m/z 557 and 149). These distinctive fragments were further validated by using a computer program that predicts logical mass fragments and performing GC-MS of deuterated PFPA-atenolol and PFPA-propranolol and of the PFPA-alpha-hydroxy metabolite of metoprolol. By using the unique mass fragments, none of the pilot fatality cases were found to contain more than one beta-blocker. Therefore, these mass ions can be used for differentiating and simultaneously analyzing these structurally similar beta-blockers in biological samples.

Enantiomeric determination of ephedrines and norephedrines by chiral derivatization gas chromatography-mass spectrometry approaches.

Concerned with variations in abuse potential and control status among various isomers of ephedrines and norephedrines, this study was conducted to develop an effective method for the simultaneous analysis of eight ephedrine-related compounds along with structurally similar cathinones. Among various approaches studied, a 60-m HP-5MS (0.25 mm i.d., 0.25 microm film thickness) was successfully used to characterize the following compounds that were derivatized with (-)-alpha-methoxy-alpha-trifloromethylphenylacetic acid (MTPA): (+)-cathinone, (-)-cathinone, (+)-norephedrine, (-)-norephedrine, (+)-norpseudoephedrine, (+)-ephedrine, (-)-ephedrine, (-)-pseudoephedrine, (+)-pseudoephedrine. (-)-Cathine standard was not available, but should also be resolvable under this analytical procedure. This method was successfully applied to the analysis of selected cold remedies for characterizing the enantiomeric compositions of the compounds present in these samples.

Utilizing the urinary 5-HTOL/5-HIAA ratio to determine ethanol origin in civil aviation accident victims.

Specimens from fatal aviation accident victims are submitted to the FAA Civil Aerospace Medical Institute for toxicological analysis. During toxicological evaluations, ethanol analysis is performed on all cases. Care must be taken when interpreting a positive ethanol result due to the potential for postmortem ethanol formation. Several indicators of postmortem ethanol formation exist; however, none are completely reliable. The consumption of ethanol has been shown to alter the concentration of two major serotonin metabolites, 5-hydroxytryptophol (5-HTOL) and 5-hydroxyindole-3-acetic acid (5-HIAA). While the 5-HTOL/5-HIAA ratio is normally very low, previous studies using living subjects have demonstrated that the urinary 5-HTOL/5-HIAA ratio is significantly elevated for 11-19 h after acute ethanol ingestion. Recently, our laboratory developed and validated an analytical method for the simultaneous determination of both 5-HTOL and 5-HIAA in forensic urine samples using a simple liquid/liquid extraction and LC/MS/MS and LC/MS/MS/MS. In this previous work a 15 pmol/nmol serotonin metabolite ratio cutoff was established in postmortem urine, below which it could be conclusively determined that no recent antemortem ethanol consumption had occurred. In the current study this newly validated analytical method was applied to five ethanol-positive aviation fatalities where the origin of the ethanol present could not previously be conclusively determined. In four of the five cases examined the detected ethanol was demonstrated to be present due to postmortem microbial formation, and not consumption, even though some indication of ethanol consumption may have been present.

Determination of select antidepressants in fish from an effluent-dominated stream.

Increasing evidence indicates widespread occurrence of pharmaceuticals and personal care products (PPCPs) in municipal effluent discharges and surface waters. Studies that characterize the fate and effects of PPCPs in aquatic systems are limited, and to our knowledge, data regarding pharmaceutical accumulation in fish of effluent-dominated ecosystems have not been previously reported. In the present study, fish populations were sampled from a reference stream and an effluent-dominated stream in north Texas, USA. Lepomis macrochirus, Ictalurus punctatus, Cyprinus carpio, and Pomoxis nigromaculatus were killed; the liver, brain, and lateral filet tissues dissected; and the tissues stored at -80 degrees C until analysis. Fish tissues were extracted using solid-phase extraction and then analyzed by gas chromatography-mass spectrometry in the negative chemical ionization mode. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and sertraline and the SSRI metabolites norfluoxetine and desmethylsertraline were detected at levels greater than 0.1 ng/g in all tissues examined from fish residing in a municipal effluent-dominated stream. To our knowledge, the present study is the first report of SSRI residues in fish residing within municipal effluent-dominated systems.