Method for isolation and determination of pyridostigmine and metabolites in urine and blood

Ellin, Robert I.; Zvirblis, Peter; Wilson, Michael

doi:10.1016/s0378-4347(00)80436-3

Cited by 40 publications

(15 citation statements)

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“…Additionally, decreased l'.r operant response rate, deficit in role mode performance and a decrease in turning-wheel activity has been observed [6,14]. Studies by Crofton and Reiter [9] have shown a decrease in locomotor activity in rats exposed to permethrin. [6] Bloom, A.S., Staatz, CG.…”

Section: Discussionmentioning

confidence: 99%

“…Eilin et al [9] reported linear range between 40 and 500 ng/ml for DEET in plasma using HPLC, while Yaylor et al [14] reported a linearity over a range between 19 and 1910 ng/ml for DEET using gas chromatography (GC). Also, Chan et al [38] reported a linear range for pyridostigmine bromide in human plasma over concentrations between 50 and 1000 ng/ml.…”

Section: Discussionmentioning

confidence: 99%

“…PII: S0378-4347(00)00407-2 veterans, and permethrin was sprayed against orthropod vectors on the battle dress uniforms [35]. Pyridostigmine bromide has been reported to be absorbed into plasma and excreted in urine following oral or intravenous dose in rat [9,10,17,18,27,29,36], in man [16,24], and in dog [15,28]. Absorption and excretion of DEET and metabolites were rapid after dermal application in human [11,13], in rats [19], and in dogs [14].…”

Section: Introductionmentioning

confidence: 99%

“…Several analytical methods have been used for identification and quantification of the above chemicals and their metabolites, when applied alone in plasma and urine samples. These methods used highperformance liquid chromatography (HPLC) [9,[11][12][13][14]25,34], HPLC-mass spectrometry [19], gas chromatography [21][22][23][24][39][40][41], gas chromatographymass spectrometry [26,32,38,42], and thin layer chromatography [22,30,31]. Other techniques were also used, e.g.…”

Section: Introductionmentioning

confidence: 99%

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Toxic Interactions of Prophylactic Drugs and Pesticides

Abou‐Donia¹

2003

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Approved for public release; Distribution unlimited 12b. DISTRIBUTION CODE ABSTRACT (Maximum 200 Words/The goal of the present project is to define the mechanisms of neurotoxic interactions following exposure to pyridostigmine bromide (PB, 0.13, 1.3,13 mg/gk in water, oral), DEET (4.0, 40.0, 400.0 mg/kg in ethanol, dermal), and permethrin (0.013, 0.13, 1.3 mg/kg in ethanol, dermal) in male Sprauge-Dawley rats. The results are summarized below. 1. Combined exposure to the three test compounds for 28 days, alone or with stress produced neuropathological alterations in the brain and hepatic lesions. 2. The same treatments increased the permeability of the blood brain barrier (BBB), as assessed by [ 3 H]hexamethonium iodide uptake and horseradish peroxidase (HRP) staining.3. Specific brain region exhibited decreased activity of AChE and ligand binding of m2 muscarinic acetylcholine receptors. 4. Exposure to DEET alone, or with permethrin significantly increased urinary excretion of 8-hydroxy-2'-deoxyguanosine. 5. Within 30 minutes of dermal application of 400 mg/kg DEET alone, or in combination with 1.3 mg/kg permethrin, 55% DEET and 38% permethrin was absorbed. Distribution of permethrin in tissues was slower than DEET.Combined application to both chemicals increased AUC for DEET but did not affect AUC FlasT . a of permethrin. The goal of this project is to evaluate the possible interaction between DEET, permethrin and pyridostigmine bromide (PB) and the biological and pathological consequences of such interactions. Our standing hypothesis is that combined exposure to a mixture of chemicals would have enhanced, and in some cases deterimental toxicological effects than exposure with single chemical. SUBJECT TERMS B) ApproachWe have been testing the stated hypothesis that interactions between combined chemical exposure would result in greater toxicological and pathological changes, and certain environmental modifying factors such as stress would modulate the toxic effects in combined exposure scenario. In the previous year we have carried out dose-response studies ranging from 0.1-10 x the estimated human exposure on DEET, permethrin and PB. In those studies we carried out neurobehavioral as well as neurochemical assessment following exposure to a single or multiple chemicals (See the manuscripts in Appendix). In the current studies, we have focused on the pathological consequences of sub-chronic exposure to single chemical or combined concurrent exposure. Additionally, we studied the effect of one environmental modifier, stress on the neurotoxicity associated with concurrent exposure to PB, DEET and permethrin. The pathological changes were studied by immunohistochemical evaluation of microtubule-associated protein-2 (MAP-2), glialfibrillary acidic protein (GFAP), and microglial activation by lectin binding. Furthermore, we evaluated the possible mechanism(s) of neurotoxic effects of single or combined exposure by assessing the permeability of blood-brain barrier (BBB) and evaluating 8-hydroxy-2'-deoxyguanosine by ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Toxic Interactions of Prophylactic Drugs and Pesticides

Abou‐Donia¹

2003

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“…The concentration of PB and its persistence in the nutrient medium was measured by gas chromatography/mass spectrophotometer (GC/MS). 8 For examination by light microscopy, the neuromuscular junctions were localized using the histochemical method of Karnovsky and Roots for detection of cholinesterase, 15 and the axons were visualized by a Holmes silver impregnation counterstain. 27 For ultrastructural studies, spinal cordmuscle cocultures were incubated in cold calcium/ magnesium-free phosphate buffer with 5 mmol/L EGTA for 1 h to prevent contraction of muscle during fixation.…”

Section: Methodsmentioning

confidence: 99%

Effects of exposure to low-dose pyridostigmine on neuromuscular junctions in vitro

Drake-Baumann

Seil

1999

Muscle Nerve

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Stability indicating reversed‐phase‐high‐performance liquid chromatography method development and validation for pyridostigmine bromide and sodium benzoate in oral solution

Chintala

2023

Biomedical Chromatography

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The present study focuses on the development of a simple, rapid, specific, and stability‐indicating HPLC method for the simultaneous analysis of pyridostigmine bromide (PGB) and sodium benzoate (SBN) in oral liquid dosage forms. Analytical techniques should enhance sensitivity and specificity for the estimation of pharmaceutical drug products. Stress studies were conducted under various International Conference on Harmonization (ICH) conditions for evaluation. The further optimized HPLC method was validated in accordance with the current ICH guidelines. Chromatographic separation was accomplished using a mobile phase consisting of a 950:50 v/v ratio of perchloric acid buffer and acetonitrile as mobile phase‐A, and 100% acetonitrile as mobile phase‐B. The flow rate is 1.0 mL/min, and the injection volume is 20 μL. Detection of components was carried out at 220 nm for PGB and 228 nm for SBN. The validated HPLC method demonstrated high specificity, with linearity ranging between 24 and 72 μg/mL for PGB and 5.2–15.6 μg/mL for SBN. The correlation coefficient for both drugs exceeded 0.999. The method demonstrated high accuracy, exceeding 97%. In stress studies, PGB was found to be sensitive to alkaline stress conditions. The results reveal the successful applicability of the current method for the estimation of PGB and SBN in its marketed formulation, which can be reasonably inferred to assess other formulation systems.

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Method for isolation and determination of pyridostigmine and metabolites in urine and blood

Cited by 40 publications

References 9 publications

Toxic Interactions of Prophylactic Drugs and Pesticides

Toxic Interactions of Prophylactic Drugs and Pesticides

Effects of exposure to low-dose pyridostigmine on neuromuscular junctions in vitro

Stability indicating reversed‐phase‐high‐performance liquid chromatography method development and validation for pyridostigmine bromide and sodium benzoate in oral solution

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