RESUMO
The objective of this study was to establish the pharmacokinetics of a single oral dose of trazodone in the Hispaniolan Amazon parrot (Amazona ventralis). Trazodone is a selective serotonin antagonist and reuptake inhibitor used commonly in both human and veterinary medicine as an antidepressant behavioral modification medicine. A single oral dose of compounded trazodone hydrochloride solution (20 mg/mL) at 50 mg/kg was administered to a total of 7 healthy adult Hispaniolan Amazon parrots. The 7 healthy adult parrots ranged in age from 10 to 15 years and weighed 228 to 323g. Blood was collected at baseline (2 weeks before study) and at 1, 2, 4, 6, 10, and 14 hours post-drug administration. Plasma concentrations of both trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were measured via liquid chromatography tandem mass spectrometry. Noncompartmental pharmacokinetic analysis was completed. The half-life (t1/2) ± SD of trazodone for the Hispaniolan parrots was 1.89 ± 0.49 hours, and the t1/2 ± SD of mCPP metabolite was 1.9 ± 0.55 hours. Maximum serum drug concentrations, or Cmax (ng/mL), were 738.3 ± 285.3 for trazodone. Times to achieve Cmax (hours) for trazadone and the mCPP metabolite were 1 hour and 2 hours postdosing, respectively. While this study did not establish the behavioral effects of trazodone, no adverse side effects were observed throughout the 48-hour period following drug administration and blood collection. Our results indicate that the oral administration of a 50-mg/kg single dose of trazodone to Hispaniolan parrots may be considered a safe dose. Plasma concentrations are comparable to previously published values in humans, dogs, horses, and pigeons (Columba livia domestica) for up to 14 hours following dosing. This study indicates that further studies are needed to establish the pharmacodynamics and the efficacy of trazodone in the medical management of behavioral problems in psittacine species.
Assuntos
Amazona , Trazodona , Animais , Trazodona/farmacocinética , Trazodona/administração & dosagem , Trazodona/sangue , Amazona/sangue , Meia-Vida , Masculino , Área Sob a Curva , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/sangue , Feminino , Administração OralRESUMO
Invasive fungal aspergillosis is a leading cause of morbidity and mortality in many species including avian species such as common ravens (Corvus corax). Methods were developed for mass spectral determination of voriconazole in raven plasma as a means of determining pharmacokinetics of this antifungal agent. Without further development, GC/MS/MS (gas chromatography-tandem quadrupole mass spectrometry) proved to be inferior to LC/MS/MS (liquid chromatography-tandem quadrupole mass spectrometry) for measurement of voriconazole levels in treated raven plasma owing to numerous heat-induced breakdown products despite protection of voriconazole functional groups with trimethylsilyl moieties. LC/MS/MS measurement revealed in multi-dosing experiments that the ravens were capable of rapid or ultrarapid metabolism of voriconazole. This accounted for the animals' inability to raise the drug into the therapeutic range regardless of dosing regimen unless cytochrome P450 (CYP) inhibitors were included. Strategic selection of CYP inhibitors showed that of four selected compounds including cimetidine, enrofloxacin and omeprazole, only ciprofloxacin (Cipro) was able to maintain voriconazole levels in the therapeutic range until the end of the dosing period. The optimal method of administration involved maintenance doses of voriconazole at 6 mg/kg and ciprofloxacin at 20 mg/kg. Higher doses of voriconazole such as 18 mg/kg were also tenable without apparent induction of toxicity. Although most species employ CYP2C19 to metabolize voriconazole, it was necessary to speculate that voriconazole might be subject to metabolism by CYP1A2 in the ravens to explain the utility of ciprofloxacin, a previously unknown enzymatic route. Finally, despite its widespread catalog of CYP inhibitions including CYP1A2 and CYP2C19, cimetidine may be inadequate at enhancing voriconazole levels owing to its known effects on raising gastric pH, a result that may limit voriconazole solubility.
Assuntos
Antifúngicos , Inibidores das Enzimas do Citocromo P-450 , Espectrometria de Massas em Tandem , Voriconazol , Voriconazol/farmacocinética , Animais , Antifúngicos/farmacocinética , Inibidores das Enzimas do Citocromo P-450/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Cromatografia LíquidaRESUMO
The Humboldt penguin (Spheniscus humboldti) population at the Punta San Juan Marine Protected Area in Peru is considered critical to the long-term sustainability of this endangered species in Peru. Exposure of the rookery to environmental toxicants is a mounting concern because of regional growth of industries and human populations. Whole blood samples were collected from 30 free-ranging penguins in 2011 as part of a broader population health monitoring program. Dried blood spots (DBS) containing 50 µl of blood were prepared and analyzed to assess exposure to five groups of environmental contaminants. Concentrations of elements arsenic, cadmium, iron, lead, mercury, selenium, and thallium were analyzed using inductively coupled plasma mass spectrometry. Persistent organic pollutant concentrations were measured using gas chromatography-tandem mass spectrometry to analyze organochlorine pesticides (OCP; p,p'-DDT, p,p'-DDE, ß-hexachlorocyclohexane, t-nonachlor, and oxychlordane), polychlorinated biphenyls (congeners 138 and 153), and polybrominated flame retardants (polybrominated biphenyl-153 and polybrominated diphenyl ether congeners 47 and 99). Per- and polyfluoroalkyl substances, including perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid were measured using liquid chromatography-tandem mass spectrometry. Results revealed low levels of exposure to these selected contaminants, at levels not considered to be of concern for wildlife health. DBS methodology was considered effective in a field-based setting for quantification of whole blood concentrations of environmental contaminants in penguins.
Assuntos
Spheniscidae , Animais , Humanos , Peru , Poluentes Orgânicos Persistentes , Animais Selvagens , Cromatografia Líquida/veterinária , DDT , Diclorodifenil DicloroetilenoRESUMO
Torsional stress in double-stranded DNA enables and regulates facets of chromosomal metabolism, replication, and transcription and requires regulatory enzymatic systems including topoisomerases and histone methyltransferases. As such, this machinery may be subject to deleterious effects from reactive mutagens, including ones from carcinogenic polycyclic aromatic hydrocarbon (PAH) adduct formation with DNA. Supercoiled plasmid DNA was investigated for its torsional responses to adducts formed in vitro from PAH benzylic carbocation reactive intermediates created spontaneously by release of leaving groups. PAH sulfate esters were found to (1) unwind DNA in a concentration dependent manner, and (2) provide maximum unwinding in a pattern consistent with known carcinogenicities of the parent PAHs, that is, 6-methylbenzo[a]pyrene > 7,12-methylbenz[a]anthracene > 3-methylcholanthrene > 9-methylanthracene > 7-methylbenz[a]anthracene > 1-methylpyrene. Supercoil unwinding was demonstrated to be dependent on the presence of sulfate or chloride leaving groups such that reactive carbocations were generated in situ by hydrolysis. In silico modeling of intercalative complex topology showed PAH benzylic carbocation reactive functional groups in alignment with target nucleophiles on guanine bases in a 5'-dCdG-3' pocket in agreement with known formation of nucleotide adducts. Inhibitory or modulatory effects on PAH-induced supercoil unwinding were seen with ascorbic acid and an experimental antineoplastic agent Antineoplaston A10 in agreement with their known anticarcinogenic properties. In summary, the reactive PAH intermediates studied here undoubtedly participate in well-known mutational mechanisms such as frameshifts and apurinic site generation. However, they are also capable of random disruption of chromosomal supercoiling in a manner consistent with the known carcinogenicities of the parent compounds, and this mechanism may represent an additional detrimental motif worthy of further study for a more complete understanding of chemical carcinogenicity.
Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , DNA/metabolismo , Antracenos , Sulfatos , Desoxirribonucleotídeos , Adutos de DNARESUMO
BACKGROUND: Dried blood spot (DBS) technology is valuable in providing simple means of storing blood samples from wildlife with small blood volumes. Methods designed for heavy metal analysis on DBS become more useful if extended to elements of nutritional significance. PURPOSE: (1) Development of procedures for measuring Mn, Fe, Co, Cu, Zn, Se and Mo in DBS; (2) use the designed methods in health assessments of Galápagos land iguanas (Conolophus species). PROCEDURES: Elements were measured by inductively coupled plasma/mass spectrometry (ICP-MS) following acid digestion of whole blood or DBS from the same animal for direct comparison. Study animals comprised free-ranging iguanas from separate islands in the Galápagos archipelago. MAIN FINDINGS: DBS spikes (Mn, Fe, Co, Cu, Zn, Se and Mo) demonstrated accuracy to â¼100 ppb; reporting limits were set there except for Fe and Zn which were set at 1000 ppb. Plasma samples - generally preferable for nutritional element diagnostics - were submitted from Galápagos land iguanas along with DBS as part of a large-scale health assessment. In plasma versus DBS concentration comparisons, Fe, Cu, Se and Mn correlated well with R^2 values of 0.799, 0.818, 0.896 and 0.899, respectively, and slopes ranging 0.88 - 1.3. Co and Zn showed greater scatter. Mo had insufficient points above its reporting limit and offered advantages for toxicity assessments. Bland-Altman diagrams showed flat scatter between 2x standard deviation boundaries with no undue trends except for Mn which had few points above its reporting limit. Bias, defined as the average difference [DBS - plasma] divided by the average value, was relatively low throughout, with values of - 19.3 % (Fe), - 48.7 % (Co), - 19.6 % (Cu), - 6.9 % (Zn), - 21.4 % (Se) and + 40.7 % (Mn). Normal distribution assessment of iguana Cu, Zn, Se and Fe plasma values showed unanticipated divergences between two species. CONCLUSIONS: The DBS approach for nutritional element analysis offers a suitable methodology for determining crucial elements Mn, Fe, Co, Cu, Zn, Se, and Mo in veterinary samples. Analyses of samples from Conolophus species revealed interesting divergences particularly for Cu, Zn, Se and Fe, elements generally associated with defense against oxidative stress.
Assuntos
Iguanas , Metais Pesados , Oligoelementos , Animais , Oligoelementos/análise , Teste em Amostras de Sangue Seco , Análise EspectralRESUMO
Metaldehyde consumption by pets and other mammals constitute medical emergencies ideally requiring rapid poison removal. The purpose of this study was three-fold: 1) development of a sensitive method for metaldehyde quantitation in patient serum samples by gas chromatography combined with tandem quadrupole mass spectrometry (GC/MS/MS); 2) development of a sensitive method for quantitation of the volatile metaldehyde metabolite acetaldehyde by headspace analysis combined with GC/MS/MS; and 3) an initial assessment of the efficacy of combined dialysis and hemoperfusion treatments in diminishing toxin loads in canine victims of metaldehyde poisoning. Both mass spectrometric approaches relied on Multiple Reaction Monitoring (MRM) methodologies. Metaldehyde extracted via liquid-liquid partitioning from serum was detected with a limit of quantitation (LOQ) of 7.3 ± 1.4 ng/mL with linearity in the range 1-250 ng/mL with accuracy improved by inclusion of a deuterated metaldehyde internal standard. Acetaldehyde was determined to have an LOQ of 0.39 µg/mL with linearity in the range 1-1000 µg/mL. The developed methodologies were applied to canine samples taken over various time points during dialysis treatment. Two of three canine patients showed significant abatement of metaldehyde levels by over 50-fold from initial concentrations while a third was shown to be negative with no measureable metaldehyde. The toxic metabolite acetaldehyde was found in one of the metaldehyde-poisoned patients and the detected acetaldehyde was also reduced by roughly 200-fold during the course of treatment. The designed mass spectrometric techniques were thus successful in demonstrating the efficacy of the applied dialysis-hemoperfusion methods which may find wider applicability against other potentially lethal toxins in poisoned patients in future studies.
Assuntos
Acetaldeído , Espectrometria de Massas em Tandem , Humanos , Animais , Cães , Cromatografia Gasosa-Espectrometria de Massas , Acetaldeído/análise , Diálise Renal , MamíferosRESUMO
Anabolic androgenic steroids are synthetic substances related to the male sex hormones (androgens). These agents promote the growth of skeletal muscle (anabolic effects) and the development of male sexual characteristics (androgenic effects). Anabolic steroids have been illegally used for many years as performance-enhancing drugs in human, equine, and canine sports and as growth promoters in livestock reared to provide meat for human consumption. The analytical challenge to developing effective means of control within these fields has been exacerbated by the reported endogenous nature of some of these steroids. Anabolic steroids have been employed extensively in equine practice over the past 50 years. Their usefulness is largely dependent on subjective opinions, as only minimal studies investigating pharmacodynamics have been carried out in horses. Therefore, their use will vary markedly between practitioners depending on their personal experiences and pressures by trainers to use them. They form part of rational therapy in a variety of conditions. In addition to their use for increasing muscle mass, they are used to varying extents in the raising of yearlings and in the training and racing of horses with the view of improving performance. The use of these agents is prohibited in the horseracing industry by the Association of Racing Commissioners International (ARCI), International Federation of Horseracing Authorities (IFHA), and Fédération Equestre Internationale (FEI).
Assuntos
Anabolizantes , Dopagem Esportivo , Nandrolona , Cavalos , Animais , Masculino , Cães , Humanos , Esteróides Androgênicos Anabolizantes , Nandrolona/farmacologia , Testosterona , Androgênios/farmacologia , Esteroides/química , Anabolizantes/farmacologia , Anabolizantes/químicaRESUMO
Based on structural similarities and equine administration experiments, Barbarin, 5-phenyl-2-oxazolidinethione from Brassicaceae plants, is a possible source of equine urinary identifications of aminorex, (R,S)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine, an amphetamine-related US Drug Enforcement Administration (DEA) controlled substance considered illegal in sport horses. We now report the synthesis and certification of d5 -barbarin to facilitate research on the relationship between plant barbarin and such aminorex identifications. D5 -barbarin synthesis commenced with production of d5 -2-oxo-2-phenylacetaldehyde oxime (d5 -oxime) from d5 -acetophenone via butylnitrite in an ethoxide/ethanol solution. This d5 -oxime was then reduced with lithium aluminum hydride (LiAlH4 ) to produce the corresponding d5 -2-amino-1-phenylethan-1-ol (d5 -phenylethanolamine). Final ring closure of the d5 -phenylethanolamine was performed by the addition of carbon disulfide (CS2 ) with pyridine. The reaction product was purified by recrystallization and presented as a stable white crystalline powder. Proton NMR spectroscopy revealed a triplet at 5.88 ppm for one proton, a double doublet at 3.71 ppm for one proton, and double doublet at 4.11 ppm for one proton, confirming d5 -barbarin as the product. Further characterization by high resolution mass spectrometry supports the successful synthesis of d5 -barbarin. Purity of the recrystallized product was ascertained by High Performance Liquid Chromatography (HPLC) to be greater than 98%. Together, we have developed the synthesis and full characterization of d5 -barbarin for use as an internal standard in barbarin-related and equine forensic research.
Assuntos
Aminorex , Prótons , Animais , Cavalos , Oxazóis , Espectrometria de MassasRESUMO
OBJECTIVE: To determine the pharmacokinetics of voriconazole after single IV or orally administered boluses in common ravens (Corvus corax). ANIMALS: 8 healthy common ravens. PROCEDURES: Voriconazole (5 mg/mL, 10 mg/kg IV) was administered to 8 birds, and then plasma voriconazole concentrations were measured at various time points by high-pressure liquid chromatography with mass spectrometry. Starting 6 months later in a randomized 3-treatment 3-period regimen, birds received a single oral dose of voriconazole suspension (10 mg/mL; 6, 12, and 24 mg/kg PO). The study period was May 2015 to March 2016. RESULTS: Voriconazole (10 mg/kg IV) achieved an initial plasma concentration of 6.31 µg/mL when measured over 21 hours. After oral administration of voriconazole at 6, 12, and 24 mg/kg, the relative bioavailability was 67.5%, 209%, and 183%, respectively. For the 6-mg/kg dose, the maximum plasma concentration was reached at 30 minutes after administration and remained in the therapeutic range of 0.5 to 1 µg/mL for approximately 15 hours. The 12- and 24-mg/kg doses resulted in concentrations in a potentially toxic range. CLINICAL RELEVANCE: Voriconazole was well tolerated. All 4 doses resulted in plasma concentrations of voriconazole > 0.5 µg/mL, which is the minimum inhibitory concentration recommended for pathogenic species of Aspergillus fungi known to affect birds. A single dose of voriconazole administered as 10 mg/kg IV or 6 mg/kg PO resulted in recommended target plasma concentrations. Administration of voriconazole 6 mg/kg PO 2 to 3 times daily may be adequate for treatment without exceeding the toxic range.
Assuntos
Corvos , Administração Intravenosa/veterinária , Administração Oral , Animais , Antifúngicos , Área Sob a Curva , Aspergillus , Testes de Sensibilidade Microbiana/veterinária , Pirimidinas , Triazóis , VoriconazolRESUMO
A case of feline intoxication and fatality with the illicit drug heroin is described. A 5-year-old castrated male domestic shorthair cat was recently diagnosed with an active pneumonitis and left at home for a couple of days under the care of another resident. Upon return, the owner found his cat dead with strong suspicion of foul play. The cat was necropsied by a local veterinary clinic to retrieve the liver for diagnostic toxicology. The postmortem liver sample screened positive for 6-acetylmorphine and 6-acetylcodeine by gas chromatography mass spectrometry. Deconvolution techniques were applied to chromatograms, which revealed the additional presence of morphine and mirtazapine. Subsequent quantitation of mirtazapine, heroin, morphine, 6-acetylmorphine and 6-acetylcodeine was performed by gas chromatography--tandem quadrupole mass spectrometry. Although companion animal fatalities arising from toxicities are a likely consequence of drug abuse in a home, this is the first reported case of a malicious feline fatality resulting from heroin with quantitation of heroin metabolites.
Assuntos
Dependência de Heroína , Heroína , Animais , Gatos , Cromatografia Gasosa-Espectrometria de Massas , Dependência de Heroína/diagnóstico , Humanos , Fígado , Masculino , Morfina , Derivados da Morfina , Detecção do Abuso de Substâncias , Espectrometria de Massas em TandemRESUMO
RATIONALE: The analytical detection of chemical residues from sodium monofluoroacetate (MFA) ingestion in targeted predatory wildlife and in pesticide misuse incidents perpetrated against nuisance companion animals remains a concern in veterinary forensic toxicology. There is a current need for chemically stable sample extracts with reliable and specific diagnostic methods for trace quantities in diverse diagnostic matrices. METHODS: Biphasic pentafluorobenzylation provided a simple combined extraction and derivatization procedure for removing MFA in a chemically stable form from a complex matrix such as stomach contents. Analysis of the derivatized extract using gas chromatography/tandem quadrupole mass spectrometry (GC/MS/MS) with multiple reaction monitoring (MRM) approaches specific to MFA provided greater specificity than simple scan or selected ion monitoring approaches. RESULTS: Collision-induced dissociation in GC/MS/MS showed that pentafluorobenzyl (PFB)-derivatized MFA (M+ m/z 258) generated m/z 258â130, 149, 161, 177, 178, 180.1, and 181.1 transitions. Of these, the transition m/z 258â181 provided a peak for quantitation, whereas m/z 258â161 and 258â178 provided specificity for qualifying MFA. Similarly, PFB-derivatized 2-chloropropionic acid (M+ m/z 288) was used as an internal standard, which generated m/z 288â181 and 161. Of these, the transition m/z 288â181 provided a peak for quantitation, whereas m/z 288â161 and 181â161 served to qualify the internal standard. CONCLUSIONS: The method was validated with a calculated limit of detection of 0.35 ppm and limit of quantitation of 1.09 ppm MFA. The method should have adequate sensitivity and reliability for veterinary toxicology labs analyzing specimens from animals poisoned by this predacide.
RESUMO
Copper storage disease occurs in multiple dog breeds and is one of the most common causes of chronic hepatitis in this species. The disease is caused by hereditary defects in copper metabolism in conjunction with high dietary copper levels. The progressive copper accumulation leads to hepatitis, cirrhosis, and eventually death if left untreated. Copper chelators are critical in modulating the effects of this disease. It is therefore of significant practicality to understand the pharmacokinetic (PK) parameters of chelating agents, particularly since they are oftentimes quite expensive. A liquid chromatography-tandem mass spectrometric (LC/MS/MS) method was developed to measure plasma levels of one of the most common chelators, d-penicillamine. The compound was discovered to exist in two forms, monomeric and dimeric, and various chemical derivatizations were tried to force the compound into one form or the other. Eventually, the simplest approach was individual determination of penicillamine and its dimer, with summation of the two quantities. This enabled determination of canine PK parameters for penicillamine based on comparison of oral and intravenous administration of the drug, including time to maximum drug level (Tmax), concentration at maximum (Cmax), clearance (Cls) and volume of distribution (Vdss). The drug was found to exist predominantly in the dimeric form in plasma, which is incapable of chelating copper owing to lack of free sulfhydryl groups and must therefore provide a storage form of the drug in equilibrium with its monomeric form in vivo. Mechanisms are discussed for the electrospray-induced fragmentation of penicillamine as well as of its dimer.
Assuntos
Quelantes/farmacocinética , Cromatografia Líquida , Monitoramento de Medicamentos , Penicilamina/farmacocinética , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Administração Intravenosa , Administração Oral , Animais , Quelantes/administração & dosagem , Cães , Feminino , Masculino , Modelos Biológicos , Penicilamina/administração & dosagem , Penicilamina/sangue , Reprodutibilidade dos TestesRESUMO
RATIONALE: Haloxyfop is a pre/post-emergence herbicide with known organ toxicities and teratogenic effects in mammals. The European Union Commission on Food Safety has an established maximum residue limit of 10 µg/kg in all agricultural products including eggs. A sensitive highly specific method would be of value in determination of haloxyfop residues in foodstuffs such as eggs. METHODS: The Michigan State University Veterinary Diagnostic Lab (MSU VDL) developed a method for the extraction of haloxyfop from eggs based on popular QuEChERS (quick, easy, cheap, effective, rugged, and safe) methodologies, essentially providing acetonitrile extracts following treatment with high ionic strength additives. Extracts derivatized with trimethylsilyl (TMS) groups were examined by gas chromatography/tandem mass spectrometry using developed multiple reaction monitoring (MRM) methodology. RESULTS: The MSU VDL received eggs from chickens exposed to 760 µg/kg haloxyfop in flaxseed. Haloxyfop-TMS m/z 374â73 MRM setting enabled quantitation across the 1-50 ppb range in comparison with an ibuprofen MRM transition as internal standard. CONCLUSIONS: The determined limit of quantitation was 2.5 ng/g, and the method successfully identified haloxyfop residues in five of six batches of the chicken eggs, with nonzero values ranging from 2.7 to 14.5 ng/g. These values were consistent with flaxseed incorporation into the diet at 4-7% and known excretion into eggs at 2-3% of daily haloxyfop exposure, and establish the utility of the method in identifying regulatory noncompliance and adulteration of food sources.
Assuntos
Ovos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Resíduos de Praguicidas/análise , Piridinas/análise , Espectrometria de Massas em Tandem/métodos , Ração Animal , Animais , Galinhas , Exposição Ambiental , MichiganRESUMO
RATIONALE: Determination of phosphine exposure from zinc or aluminum phosphide fumigants continues to be a routine analytical requirement in veterinary forensic toxicology. There is a need for a more reliable and specific method than simple gas chromatography/mass spectrometry (GC/MS) analysis of sample solvent extracts, as GC/MS of extracts on capillary columns used for general screens involves significant interference from air peaks. METHODS: GC/MS/MS headspace analysis of acid-generated phosphine gas enabled study of the feasibility of devising multiple reaction monitoring (MRM) approaches to the determination of phosphine with greater specificity. RESULTS: Collision-induced dissociation in GC/MS/MS showed that phosphine generated m/z 34 â 31, 32 and 33 ion transitions by sequential proton release as well as minor transitions m/z 34 â 47, 34 â 63 and 63 â 31.5 by intermolecular collisions and double charging. Study of the formation of these product ions enabled development of MRM settings for a highly useful headspace method for phosphine detection. CONCLUSIONS: The method was validated over a working range of 5-100 ppm of phosphide generating phosphine gas which enabled retention of regular screen capillary columns without necessitating separation from air components. The method should have adequate sensitivity and reliability for veterinary toxicology laboratories confronting specimens from animals poisoned by crop fumigants.
Assuntos
Praguicidas/análise , Fosfinas/análise , Espectrometria de Massas em Tandem/métodos , Compostos de Alumínio/análise , Animais , Toxicologia Forense/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Limite de Detecção , Medicina Veterinária/métodos , Compostos de Zinco/análiseRESUMO
Persistent organic pollutants (POPs) are organic compounds of anthropogenic origin that resist atmospheric and microbial degradation and thus persist in the environment and in food chains for exceptionally long periods of time. Veterinarians and wildlife researchers need simple methodologies for monitoring and measuring such compounds including two large and diverse categories, organochlorine pesticides (OCs) and polychlorinated biphenyls (PCBs), compounds that have been largely banned from production and use except for specific exceptions. We present development of methodologies for detection and quantitation of 22 OCs and 10 PCB congeners by tandem quadrupole gas chromatography-mass spectrometric analysis of Dried Blood Spots (DBS). Development was enabled by (1) optimization of suspension and extraction methodologies for DBS; (2) strategic streamlining and condensation of Multiple Reaction Monitoring (MRM) settings on GC/MS/MS; and (3) improvement of GC settings to accommodate all 32 compounds in a single chromatographic run per sample. The method was validated for parameters of linearity, limits of detection and quantitation, recovery and precision, and results from blood were shown to correlate well with those from DBS despite both being only 50 uL in volume. The method was applied successfully to blood samples from nine avian specimens submitted to the MSU Veterinary Diagnostic Lab, and all were shown to bear the burden of varying levels of OCs and/or PCB compounds.
Assuntos
Teste em Amostras de Sangue Seco/veterinária , Monitoramento Ambiental/métodos , Poluentes Orgânicos Persistentes/sangue , Praguicidas/sangue , Bifenilos Policlorados/sangue , Animais , Aves/sangue , Calibragem , Bovinos , Cromatografia Gasosa-Espectrometria de Massas , Reprodutibilidade dos Testes , Espectrometria de Massas em TandemRESUMO
The presence of measurable quantities of arsenic in the blood of most terrestrial species signifies an exposure that often warrants further investigation regarding source and potential veterinary intervention and treatment. However, some species, such as felids, have a genetic predisposition to retain arsenic in their blood; circulating concentrations of the heavy metal, albeit abnormal for most species, may actually present as a normal or expected finding. To make sense of this disparity, the authors queried a veterinary diagnostic laboratory database over a time period of 10 years (2008-2018) to discern the range of arsenic concentrations observed in various felids. All felid whole blood samples tested for heavy metals contained measurable concentrations of arsenic; this contrasts with other companion animals such as dogs which generally had arsenic concentrations below detectability. From these data, the authors present a working reference interval for whole blood arsenic in both domestic and captive-raised big cats. Veterinary diagnostic reference intervals are important parameters for the clinical management of animal health. Reference intervals for enzymes, hormones, minerals, vitamins and therapeutic drugs specific to organ function and health are becoming increasingly well defined for most companion and production animal species, and often dictate the clinician's decisions regarding therapeutic approaches. A conundrum arises, however, when the presence or detection of a heavy metal that is otherwise deemed potentially 'toxic' to most species is an 'expected', or 'normal', finding in another. Such is the case with whole blood heavy metal screens for the feline patient. The presence of blood arsenic is a common finding in both domestic and big cats raised in captivity. If not placed into the context of a range of known results, the finding may be erroneously interpreted as evidence for acute heavy metal intoxication. The current study reviews feline whole blood heavy metal submissions for arsenic concentrations to the Michigan State University Veterinary Diagnostic Laboratory between 2008 and 2018.
Assuntos
Arsênio/sangue , Gatos/sangue , Animais , Técnicas de Laboratório Clínico/veterinária , Bases de Dados FactuaisRESUMO
During an avian mass mortality event investigation at the National Fish and Wildlife Forensic Laboratory in Ashland, OR, imidacloprid became an insecticide of concern. A qualitative analytical toxicology screen of seeds, plucks (tongue, esophagus, and trachea), and ventricular contents was requested. A method for the extraction and qualitative analysis of the insecticide in animal tissues was therefore developed. The procedure relies on a combined Food Emergency Response Network (FERN) and QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) approach to sample extraction followed by qualitative analysis by gas chromatography-tandem mass spectrometry. Since imidacloprid is not amenable to the conditions of gas chromatography, a trimethylsilyl derivative was created and characterized. Proposed mechanisms for the creation of this derivative and its mass spectrum are described. The imidacloprid-trimethylsilyl (TMS) derivative was detected in all samples submitted.
Assuntos
Aves , Toxicologia Forense/métodos , Neonicotinoides/análise , Nitrocompostos/análise , Patologia Veterinária/métodos , Resíduos de Praguicidas/análise , Animais , Autopsia , Doenças das Aves/mortalidade , Toxicologia Forense/instrumentação , Cromatografia Gasosa-Espectrometria de Massas/veterinária , Neonicotinoides/intoxicação , Nitrocompostos/intoxicação , Patologia Veterinária/instrumentação , Resíduos de Praguicidas/intoxicação , Intoxicação/mortalidade , Intoxicação/veterinária , Espectrometria de Massas em Tandem/veterináriaRESUMO
A case of canine intoxication and fatality with the pyrethroid insecticide bifenthrin is described. A 5-year-old female spayed Pit Bull Terrier was off leash and unsupervised at home for 15-20 min prior to discovery by her owner. The patient was in lateral recumbency, having what the owner described as a seizure. The patient was transported to an emergency veterinary hospital where she presented with tachycardia, tachypnea and intractable tremors/seizures. Despite aggressive medical intervention, the patient went into respiratory and cardiac arrest and died at 28 h after presentation. A postmortem liver sample screened positive for bifenthrin by gas chromatography-mass spectrometry (GC-MS). During the screening procedure, four additional bifenthrin-metabolic products were also observed. Concentrations for bifenthrin were determined for fat, kidney, liver and urine by GC-MS-MS. This is the first reported case of a canine fatality resulting from bifenthrin.
Assuntos
Doenças do Cão/induzido quimicamente , Inseticidas/intoxicação , Síndromes Neurotóxicas/veterinária , Piretrinas/intoxicação , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/metabolismo , Cães , Evolução Fatal , Feminino , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas/veterinária , Inseticidas/metabolismo , Fígado/metabolismo , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo , Piretrinas/metabolismo , Convulsões/induzido quimicamente , Convulsões/diagnóstico , Convulsões/veterinária , Taquicardia/induzido quimicamente , Taquicardia/diagnóstico , Taquicardia/veterinária , Taquipneia/induzido quimicamente , Taquipneia/diagnóstico , Taquipneia/veterinária , Espectrometria de Massas em Tandem/veterinária , Distribuição Tecidual , Medicina VeterináriaRESUMO
Plasma osmolalities of marine vertebrates are generally lower than the surrounding medium; therefore, marine organisms must cope with the osmoregulatory challenges of life in a salty environment. The salt glands serve to maintain osmotic and ionic homeostasis in a number of lower marine vertebrates. One marine reptile, the leatherback sea turtle (Dermochelys coriacea), ingests excessive amounts of salts due to their diet of gelatinous zooplankton. Outside of the normal osmoregulatory function of the salt gland, little research has been conducted on contaminant accumulation and excretion in this organ. Here, we established arsenic, cadmium, lead, mercury, and selenium concentrations in red blood cells (RBCs) and salt gland secretions (SGSs) of nesting leatherbacks. We also collected salt glands from different life stage classes of dead stranded leatherbacks from the western Atlantic Ocean to determine if inorganic contaminants accumulate in this organ. Using non-metric multidimensional scaling and regression analyses, we determined that RBC and SGS inorganic contaminant concentrations were not correlated. Additionally, RBCs showed significantly higher concentrations of these contaminants in comparison to SGSs, likely due to the affinity of inorganic contaminants for the heme group of RBCs. Lastly, we found that salt gland cadmium and mercury concentrations tended to increase with increasing curved carapace length (CCL) in stranded leatherbacks. Our results indicate that different physiological mechanisms determine the distribution of inorganic contaminants in blood and SGSs. Increases in salt gland contaminant concentrations with increasing CCL suggest this organ as a potential target for accumulation.
Assuntos
Eritrócitos/química , Glândula de Sal/metabolismo , Tartarugas/anatomia & histologia , Animais , Arsênio/análise , Oceano Atlântico , Cádmio/análise , Mercúrio/análise , Selênio/análise , Tartarugas/sangueRESUMO
In 2017, a commercially available dog food was found by our laboratory to be adulterated with the euthanasia drug pentobarbital. An FDA class 1 voluntary recall by the company ensued. Since there is no set tolerance for pentobarbital in food or feed, a sensitive method for its detection was required. We describe a simple, yet efficient, method for the extraction and quantitative analysis of the barbiturate in dog food. The procedure relies on a combined food emergency response network (FERN) and QuEChERS (quick, easy, cheap, effective, rugged, and safe) approach to sample extraction followed by quantitative analysis by gas chromatography-tandem mass spectrometry (GC/MS/MS) using pentobarbital- d5 as an internal standard. This procedure improves upon other GC/MS methodologies in that derivatization of pentobarbital or its deuterated internal standard is unnecessary, and sensitivity to a calculated limit of detection (LOD) of 0.6 ppb and a limit of quantitation (LOQ) of 2 ppb is achieved.