Gas chromatography nitrogen phosphorous detection (GC-NPD) assay of tofisopam in human plasma for pharmacokinetic evaluation

Tóth, Mária; Bereczki, Andrea; Drabant, Sándor; Nemes, Katalin; Varga, Bálint; Grézal, G.; Tömlo, Judit; Lakner, G; Klebovich, Imre

doi:10.1016/j.jpba.2006.03.033

Cited by 11 publications

(6 citation statements)

References 13 publications

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“…The apparent volume of distribution ranged from 523.8 to 5,154.1 l −1 indicating that tofisopam has higher concentration in extravascular tissue than in the vascular compartment. The half-life was found to be in the range of 4 h, indicating that upon three times daily administration of 100 mg some accumulation can be expected (Tóth et al 2006). These data indicate that the steady-state tissue concentration can be expected to be in the range of or even higher than the IC 50 of PDE-4, PDE-10, and potentially also PDE-2 resulting in a partial block of these enzymes.…”

Section: Discussionmentioning

confidence: 99%

The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis

Rundfeldt¹,

Socała

Właź

2010

J Neural Transm

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Tofisopam is a member of the 2,3-benzodiazepine compound family which is marketed for the treatment of anxiety in some European countries. In contrast to classical 1,4-benzodiazepines, the compound does not bind to the benzodiazepine binding site of the γ-aminobutyric acid receptor and its psychopharmacological profile differs from such compounds. In addition to anxiolytic properties, antipsychotic effects are reported. We now show that tofisopam, 50 mg/kg intraperitoneally (i.p.), administered in parallel to repeated doses of dizocilpine 0.2 mg/kg i.p. can ameliorate dizocilpine-induced prolongation of immobility, which is considered to be a model of negative symptoms of psychosis. We further show that tofisopam acts as an isoenzyme-selective inhibitor of phosphodiesterases (PDEs) with highest affinity to PDE-4A1 (0.42 μM) followed by PDE-10A1 (0.92 μM), PDE-3 (1.98 μM) and PDE-2A3 (2.11 μM). The data indicate that tofisopam is an interesting candidate for the adjuvant treatment of psychosis with focus on negative symptoms. Combined partial inhibition of PDE-4 and PDE-10 as well as PDE-2 may be the underlying mechanism to this activity. Due to the good safety profile of tofisopam as evident from long-term use of this agent in patients, it may be concluded that dual or triple inhibition of PDE isoenzymes with additive or synergistic effects may be an interesting approach to pharmacological activity, resulting in active compounds with beneficial safety profile. Dose-limiting side effects such as emesis induced by selective inhibition of PDE-4 may be prevented by such strategies.

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Section: Discussionmentioning

confidence: 99%

The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis

Rundfeldt¹,

Socała

Właź

2010

J Neural Transm

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“…Studies were conducted to detect drugs and poisons in blood samples by gas chromatography (GC) coupled with either nitrogen phosphorous detector (Bravo, Lobos, Venegas, & Benites, ; Lizot et al, ; Mastrogianni et al, ; Tóth et al, ) or mass spectrometer (MS) (Matsuta et al, ; Meyer et al, ; Sasaki et al, ). Despite the existence of a GC–MS library, its application is limited due to its incompatibility with hydrophilic, thermolabile and non‐volatile analytes (Liu, Liu, Lin, & Ho, ; Peters & Remane, .…”

Section: Introductionmentioning

confidence: 99%

Development of a simple HPLC‐DAD multi‐analyte procedure and its application in cases evaluated by the Poison Control Center of São Paulo, Brazil

Oliveira

Zucoloto

Oliveira³

et al. 2018

Biomedical Chromatography

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This work describes a simple approach to overcome challenges in emergency toxicological analysis, using liquid-liquid extraction and high-performance liquid chromatography coupled with a diode-array detector (HPLC-DAD). A rapid procedure has been developed, for the extraction and detection of 19 analytes from the following drug classes: analgesics, benzodiazepines, antidepressants, anticonvulsants and drugs of abuse. These substances are relevant in the context of emergency toxicology in Brazil. The method has been validated according to international guidelines by establishing parameters such as lower limit of quantification, sensitivity, linearity, accuracy and precision. The intra and inter-day precision values, at the lowest concentration levels, have always been less than 20% considering its relative standard deviation. As for accuracy values, these have also been satisfactory (above 81.3%). This method was successfully applied in 201 blood samples from patients with suspected poisoning of the Poison Control Center of São Paulo (PCC-SP), Brazil. Finally, the developed method has shown to be relevant for emergency toxicology due to its high sensitivity and it could be also very useful in both fields of clinical and forensic toxicology.

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“…Similarly literature search for spectrophotometric methods of Tofisopam reports the need of chromophoric reagent and fluorescence agent for its estimation. Thus, there is a need to develop simple, less time consuming and spectrophotometric method for the assay of Tofisopam in bulk and its formulation [2][3][4][5][6][7]. So, the attempt was made to develop a simple, accurate, precise, specific spectrophotometric method for the direct quantitative estimation of Tofisopam in bulk and formulation.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of Spectrophotometric Method for the Determination of Tofisopam in Bulk and Pharmaceutical Formulation

Kokane¹,

Pananchery²,

Jain³

2017

Pharm Anal Acta

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A rapid, specific UV spectrophotometric method has been developed using a solvent methanol to determine Tofisopam content in bulk and pharmaceutical formulations. At a pre-determined wavelength at 310 nm, it was proved linear in the range of 4-24 μg/ml and exhibited good correlation coefficient (R2=0.9996) and excellent mean recovery (98-102%). The method was validated statistically and parameters like linearity, precision, accuracy, specificity, and assay were studied according to International Conference on Harmonization guidelines. The obtained results proved that the method can be employed for the routine analysis of Tofisopam in bulk as well as in the commercial formulations.

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Gas chromatography nitrogen phosphorous detection (GC-NPD) assay of tofisopam in human plasma for pharmacokinetic evaluation

Cited by 11 publications

References 13 publications

The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis

The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis

Development of a simple HPLC‐DAD multi‐analyte procedure and its application in cases evaluated by the Poison Control Center of São Paulo, Brazil

Development and Validation of Spectrophotometric Method for the Determination of Tofisopam in Bulk and Pharmaceutical Formulation

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