Development and Validation of a Quantitative UHPLC–MS-MS Method for the Determination of Alpha-Chloralose in Feline Blood and Application on Blood Samples Collected from Cats with Symptoms of Alpha-Chloralose Poisoning

Windahl, Ulrika; Lundgren, Sandra; Sprycha, Margareta; Tegner, Cecilia; Dreimanis, Kristoffer; Åberg, Annica Tevell

doi:10.1093/jat/bkab087

Cited by 4 publications

(12 citation statements)

References 16 publications

(34 reference statements)

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“…A novel validated UHPLC–MS/MS method with a lowest detection limit of 30 ng/ml was used. 16 For each cat, the association between serum concentration of AC and intoxication severity score (1–4) was calculated using Spearman’s correlation. The duration of hospitalisation for each cat was noted and the median and range described for each severity score group.…”

Section: Methodsmentioning

confidence: 99%

“… 12 – 15 AC intoxication in the clinical setting is a presumptive diagnosis based on history, clinical signs and exclusion of other diseases with a similar presentation. Poisoning can be confirmed by demonstrating AC or its metabolites in blood or urine; 1 , 6 , 11 – 13 , 16 however, the availability of commercial tests has so far been limited. As there is no antidote or otherwise specific treatment for AC intoxication, treatment is supportive and symptomatic, including monitoring and maintaining a normal body temperature, minimising external stimuli and, when indicated, anticonvulsants.…”

Section: Introductionmentioning

confidence: 99%

“…A collaboration between UDS and the Swedish National Veterinary Institute was initiated, leading to the development and validation of a novel quantitative ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) analysis for the detection of AC in feline blood. 16 …”

Section: Introductionmentioning

confidence: 99%

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Alpha-chloralose poisoning in cats: clinical findings in 25 confirmed and 78 suspected cases

Tegner

Lundgren

Dreimanis

et al. 2022

Journal of Feline Medicine and Surgery

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Objectives The aim of this study was to describe the clinical picture in cats with alpha-chloralose (AC) intoxication and to confirm AC in serum from suspected cases of AC poisoning. Methods Suspected cases of AC poisoning were identified in patient records from a small animal university hospital from January 2014 to February 2020. Clinical signs of intoxication described in respective records were compiled, the cats were graded into four intoxication severity scores and hospitalisation time and mortality were recorded. Surplus serum from select cases in late 2019 and early 2020 was analysed to detect AC with a quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis, and the AC concentration was compared with the respective cat’s intoxication severity score. Results Serum from 25 cats was available for analysis and AC poisoning was confirmed in all. Additionally, 78 cats with a clinical suspicion of AC intoxication were identified in the patient records, most of which presented from September to April. The most common signs of intoxication were ataxia, tremors, cranial nerve deficits and hyperaesthesia. The prevalence of clinical signs and intoxication severity differed from what has previously been reported, with our population presenting with less severe signs and no deaths due to intoxication. The majority had a hospitalisation time <48 h, irrespective of intoxication severity score. Conclusions and relevance This study describes the clinical signs and prognosis in feline AC intoxication. There were no mortalities in confirmed cases, indicating that AC-poisoned cats have an excellent prognosis when treated in a timely manner. Recognition of AC intoxication as a differential diagnosis for acute onset of the described neurological signs in areas where AC exposure is possible may influence clinical decision-making and help avoid excessive diagnostic procedures. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and awareness about AC poisoning may avoid unnecessary euthanasia.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Alpha-chloralose poisoning in cats: clinical findings in 25 confirmed and 78 suspected cases

Tegner

Lundgren

Dreimanis

et al. 2022

Journal of Feline Medicine and Surgery

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“…In 2021 Dijkman et al described in total 39 feline cases from The Netherlands, in two case series spanning the years 2014-2020 [19,20]. In Norway, the Norwegian Veterinary Institute (NVI) verified AC-poisoning in 30 cats and four dogs in samples collected from various veterinary clinics from December 2019 to June 2020 [16], and in the year 2021, AC poisoning was confirmed in 20 individual cats using a quantitative Ultrahigh Performance Liquid Chromatography tandem Mass Spectrometry (UHPLC-MS-MS) method for analyses of serum samples [21]. Peer-reviewed scientific reports with quantitative laboratory analyses of the substance in blood, urine, or other tissues from cases of AC-poisoning in animals as well as in humans are otherwise rare.…”

Section: Introductionmentioning

confidence: 99%

“…Peer-reviewed scientific reports with quantitative laboratory analyses of the substance in blood, urine, or other tissues from cases of AC-poisoning in animals as well as in humans are otherwise rare. To the best of our knowledge, presently the study published in 2021 by Windahl et al [21] is so far the only previous study using a validated quantitative analytical method for detection of AC in feline blood samples published in peer-reviewed literature.…”

Section: Introductionmentioning

confidence: 99%

Alpha-chloralose poisoning in cats in three Nordic countries - the importance of secondary poisoning

et al. 2022

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Background Alpha-chloralose (AC) is a compound known to be toxic to various animal species and humans. In 2018 and 2019 an increase in suspected cases of AC poisoning in cats related to the use of AC as a rodenticide was reported to national veterinary and chemical authorities in Finland, Norway and Sweden by veterinarians working in clinical practices in respective country. The aims of this study were to prospectively investigate AC poisoning in cats, including possible secondary poisoning by consuming poisoned mice, and to study metabolism and excretion of AC in cats through analysis of feline urine. Methods Data on signalment, history and clinical findings were prospectively collected in Finland, Norway and Sweden from July 2020 until March of 2021 using a questionnaire which the attending veterinarian completed and submitted together with a serum sample collected from suspected feline cases of AC-poisoning. The diagnosis was confirmed by quantification of AC in serum samples. Content of AC was studied in four feline urine samples, including screening for AC metabolites by UHPLC-HRMS/MS. Bait intake and amount of AC consumed by mice was observed in wild mice during an extermination of a rodent infestation. Results In total, 59 of 70 collected questionnaires and accompanying serum samples were included, with 127 to 70 100 ng/mL AC detected in the serum. Several tentative AC-metabolites were detected in the analysed feline urine samples, including dechlorinated and oxidated AC, several sulfate conjugates, and one glucuronic acid conjugate of AC. The calculated amount of AC ingested by each mouse was 33 to 106 mg with a mean of 61 mg. Conclusions Clinical recognition of symptoms of AC poisoning in otherwise healthy cats roaming free outdoors and known to be rodent hunters strongly correlated with confirmation of the diagnosis through toxicological analyses of serum samples. The collected feline exposure data regarding AC show together with the calculation of the intake of bait and subsequent AC concentrations in mice that secondary poisoning from ingestion of mice is possible. The results of the screening for AC metabolites in feline urine confirm that cats excrete AC both unchanged and metabolized through dechlorination, oxidation, glucuronidation and sulfatation pathways.

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Evidence of a sudden increase in α‐chloralose poisoning in dogs and cats in the Netherlands between 2018 and 2021

et al. 2022

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Background After changes in European Union biocide legislation, the Dutch Poisons Information Center observed a strong increase in information requests concerning dogs and cats exposed to α‐chloralose. To investigate whether α‐chloralose‐based rodenticides are safe for non‐professional use, additional information regarding poisoning scenarios and clinical course was collected. Methods Veterinarians reporting α‐chloralose exposure over a 2.5‐year period were contacted by mail for follow‐up information concerning exposure scenario, product formulation, clinical course and treatment, and outcome. In total, information was collected for 96 dogs and 41 cats. Results Fifty‐three of 96 dogs and 17 of 19 cats known to have been exposed to α‐chloralose‐based rodenticides developed signs of central nervous system (CNS) depression or sensory‐induced CNS excitation. Mortality in dogs and cats following exposure was 1% and 18%, respectively. An additional 22 cats presented with clinical signs suggestive of α‐chloralose poisoning, with a mortality of 5%. Limitations Exposure to α‐chloralose was not confirmed by biochemical analyses. Conclusion Dogs and especially cats were at risk of poisoning from α‐chloralose. If criteria such as acute toxicity and risk of (secondary) poisoning are applied during the approval of α‐chloralose‐based rodenticides, similar to anticoagulant‐based rodenticides, it can be concluded that α‐chloralose is also not safe for non‐professional use.

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Development and Validation of a Quantitative UHPLC–MS-MS Method for the Determination of Alpha-Chloralose in Feline Blood and Application on Blood Samples Collected from Cats with Symptoms of Alpha-Chloralose Poisoning

Cited by 4 publications

References 16 publications

Alpha-chloralose poisoning in cats: clinical findings in 25 confirmed and 78 suspected cases

Alpha-chloralose poisoning in cats: clinical findings in 25 confirmed and 78 suspected cases

Alpha-chloralose poisoning in cats in three Nordic countries - the importance of secondary poisoning

Evidence of a sudden increase in α‐chloralose poisoning in dogs and cats in the Netherlands between 2018 and 2021

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