Development of a Validated Stability-Indicating High-Performance Thin-Layer Chromatographic Method for the Quantification of Levetiracetam
14 Mar 2014-Jpc-journal of Planar Chromatography-modern Tlc (Akadémiai Kiadó)-Vol. 27, Iss: 2, pp 132-139
TL;DR: The developed high-performance thin-layer chromatographic method for the analysis of LT in a tablet formulation has been developed and validated and might be useful in the quality control ofLT in the pharmaceutical industry and environmental toxicity assessments.
Abstract: Levetiracetam (LT) is an FDA-approved orally active anticonvulsant drug. A high-performance thin-layer chromatographic (HPTLC) method for the analysis of LT in a tablet formulation has been developed and validated. Separation is performed on silica gel 60 F254 with toluene-ethyl acetate-methanol, 2:1:1 (v/v/v) as mobile phase. Densitometric evaluation of the separated zone is carried out at 204 nm. There is no chromatographic interference from the tablet excipients, and compact spots are observed for LT (RF = 0.50 ± 0.02). Regressional analysis of the calibration plot revealed good linearity over the concentration range of 0.1–1.0 μg/mL. The method is validated for linearity, precision, robustness, and recovery in accordance with ICH guidelines. The LOD and LOQ were found to be 0.03 and 0.1 μg/spot, respectively. Stability was checked under acidic, alkaline, and aquatic environmental stress conditions. The drug was found to be more than 65% undegraded after 14 days of study. The developed method might be ...
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TL;DR: Piperolactam A (PL), a representative of the inchoate skeleton of aristolactAM chassis might be the source of safe and affordable antileishmanial agents for the cure of deadly Leishmania infections.
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Cites methods from "Development of a Validated Stabilit..."
...Samples were centrifuged and he PL content was assessed by developed HPTLC method as escribed earlier (Bhattacharya et al., 2014)....
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...99) with solvent system comprising of oluene-ethyl acetae-methanol (3:2:1) (Bhattacharya et al., 2014)....
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...Content of L in developed PL-HPBCD complex was assessed by HPTLC (linearty range 100–400 ng, r2 > 0.99) with solvent system comprising of oluene-ethyl acetae-methanol (3:2:1) (Bhattacharya et al., 2014)....
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TL;DR: In this article , the authors developed and validated a methodology suitable for measuring levetiracetam concentrations in human plasma and urine using ESI-LC-MS/MS for analyte detection.
Abstract: Background: Levetiracetam is an antiepileptic drug used to prevent or treat seizure in patients with severe traumatic brain injury. This study aimed to develop and validate methodology suitable for measuring levetiracetam concentrations in human plasma and urine. Methods: Plasma or urine (10 μl) samples were spiked with [2H6]-levetiracetam and processed using an acetonitrile precipitation. ESI-LC-MS/MS was employed for analyte detection. Results: The levetiracetam calibration was linear from 0.1 to 50 mg/l in a combined matrix of plasma and urine. Intra- and inter-assay imprecision and accuracy in plasma were <7.7 and 109%, and in urine were <7.9 and 108%, respectively. Conclusion: The validated method was applied to a pharmacokinetic study of levetiracetam in critically ill patients with severe traumatic brain injury.
TL;DR: This review helps researchers to get an idea about stability-indicating methods of development and validation for newer antiepileptic drugs and the characteristics of drug products that degrade under specific degradation conditions.
Abstract: In this review on the forced degradation studies on anti-epileptic drugs and the development of validated stability-indicating assay methods for drug substances and products at a condition more severe than accelerated condition (i.e. 40 ± 2°C, 75 ± 5% relative humidity), the drug substance and drug product undergo degradation is known as forced or stress degradation. To know about the impurities developed during the storage of drug products in various environmental conditions. The limit of degradation allowable is 5-20%. More than 20% of degradation is abnormal and must be investigated. Any regulatory guidelines do not mention the pH conditions for acid or base hydrolysis, the temperature for thermal degradation or the concentration of the oxidation agent. Only International Conference on Harmonization (ICH) guidelines Q1B photostability stability and states that light sources must be a combination of UV and visible light. The shortcomings of mentioned techniques with appreciation to regulatory necessities are highlighted. A systematic method for the forced degradation studies on anti-epileptic drugs such as "Topiramate, Vigabatrin, Lacosamide, Tiagabine, Levetiracetam and Zonisamide" is discussed. This review helps researchers to get an idea about stability-indicating methods of development and validation for newer antiepileptic drugs and the characteristics of drug products that degrade under specific degradation conditions.
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TL;DR: The experimental results suggest that SV2A is the binding site of LEV in the brain and that LEV acts by modulating the function of SV2 a, supporting previous indications that LEv possesses a mechanism of action distinct from that of other antiepileptic drugs.
Abstract: Here, we show that the synaptic vesicle protein SV2A is the brain binding site of levetiracetam (LEV), a new antiepileptic drug with a unique activity profile in animal models of seizure and epilepsy. The LEV-binding site is enriched in synaptic vesicles, and photoaffinity labeling of purified synaptic vesicles confirms that it has an apparent molecular mass of ≈90 kDa. Brain membranes and purified synaptic vesicles from mice lacking SV2A do not bind a tritiated LEV derivative, indicating that SV2A is necessary for LEV binding. LEV and related compounds bind to SV2A expressed in fibroblasts, indicating that SV2A is sufficient for LEV binding. No binding was observed to the related isoforms SV2B and SV2C. Furthermore, there is a high degree of correlation between binding affinities of a series of LEV derivatives to SV2A in fibroblasts and to the LEV-binding site in brain. Finally, there is a strong correlation between the affinity of a compound for SV2A and its ability to protect against seizures in an audiogenic mouse animal model of epilepsy. These experimental results suggest that SV2A is the binding site of LEV in the brain and that LEV acts by modulating the function of SV2A, supporting previous indications that LEV possesses a mechanism of action distinct from that of other antiepileptic drugs. Further, these results indicate that proteins involved in vesicle exocytosis, and SV2 in particular, are promising targets for the development of new CNS drug therapies.
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