Enantiomeric impurity determination of levetiracetam using capillary electrochromatography

Abstract

CEC was used to develop a method for the enantiomeric excess determination of levetiracetam, an antiepileptic drug. Different types of calibration curve were evaluated for use in the range between 0.01 and 1 mg/mL when aniracetam was used as an internal standard. The method gave comparable results when only the areas of the impurity were used in the calibration curve. The predicted detection and quantification limits from the S/N were 1.1 and 3.6 microg/mL, respectively. However, experimental results showed that LOD and LOQ were underestimated. Repeatability of injection was demonstrated by the RSD values obtained for retention time, resolution, ratios of the areas impurity/internal standard, and areas of impurity and internal standard individually, which were below or equal to 9.30%. The between-days variability experiments indicated that it is better to make a calibration curve daily. The finally selected calibration curves were used to test the accuracy of the developed method on bulk samples and Keppra tablets containing 250 mg levetiracetam. Both selected calibration curves performed similarly. The one using the internal standard information gave overall recoveries between 88 and 118%, while the one using areas gave results between 84 and 118%.

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levetiracetam

“…Therefore, it is not ionized in the pH range 0–14, and is classified as a neutral drug molecule. In silico log P reported values for levetiracetam are −0.67 and −0.49, indicating that it is a polar, hydrophilic molecule. It is not unusual for in silico values of log P to vary among calculations and from experimental values because the methods used to calculate log P are based on different algorithms and because in silico methods are not yet completely accurate.…”

Enantioselective capillary electrochromatography: Recent developments and new trends

“…The application of this strategy on a set of 15 acidic and 48 basic, amphoteric and neutral compounds revealed enantioselectivity for 52 of them, of which 31 had a baseline resolution. This strategy was used in a study to develop a method to enable enantiomeric impurity determinations of levetiracetam tablets [25]. Only 7 min were needed to complete this analysis, which is only half of the analysis time compared with earlier developed LC methods.…”

Pharmaceutical Impurities from Toxicological Perspective: Review

“…Ancak bu ara ürün USP'de "Safsızlık A" olarak belirtilen ve son üründe de bulunan bir yapıdır. 32 Reaktif araürünler, aslında ileri basamaklarda reaktif veya katalizörler ile reaksiyona girme potansiyeli olan ara basamaklarda oluşan yan ürün veya safsızlıklardır. Her basamakta bir ileri basamağa taşınarak AFB ile birlikte son üründe bulunurlar.…”