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Development, optimization and validation of a HPLC DAD method assaying Levetiracetam and common AED in serum

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Development, optimization and validation of a HPLC DAD method assaying Levetiracetam and common AED in serum

Rechten: Alle rechten voorbehouden

Samenvatting

Levetiracetam is a relatively new anti epileptic drug. Although manufacturers state that therapeutic drug monitoring is not necessary The Department of Clinical Toxicology and Pharmacy at Leiden University Medical Centre is encountering a sustained amount of increase of analysis requests of patient samples with Levetiracetam. As there was no in-house Levetiracetam assay, the analysis requests were all outsourced to an external laboratory.
This report describes a gradient high-perfomance liquid chromatographic (HPLC) method for the simultaneous measurement of Levetiracetam, Oxcarbazepine (OXCZBZ), 10-hydroxy dihydrocarbamazepine (10-OH-CBZ), Carbamazepine (CBZ), Carbamazepine-10,11-epoxide (CBZ-Epoxide), Dihydroxy dihydrocarbamazepine (CBZ-Diol), Phenytoin, Phenobarbital and Lamotrigine in human serum (200 μl) utilizing β-Hydroxy ethyl theophylline and Hexobarbital as internal standards. Monitoring these drugs is important, e.g. for detecting potentially toxic concentrations and therapeutic drug monitoring.
Following a liquid-liquid extraction, Levetiracetam (5-50 mg/L, R2=0.9999), Phenobarbital (5-50 mg/L, R2=0.9997), Lamotrigine (2-20 mg/L, R2=0.9982), CBZ-Diol (1-10 mg/L, R2=0.9995), 10-OH-CBZ (5-50 mg/L, R2=0.9996), CBZ-Epoxide (0,5-5 mg/L, R2=0.9998), OXCBZ (1-10 mg/L, R2=0.9997), Phenytoin (3-30 mg/L, R2=0.9997) and CBZ (2-20 mg/L, R2=0.9999) were seperated on a C18 ODS Hypersil column and eluent was monitored by Diode Array Detection at a wavelength of 210 nm. This multi anti epileptic drug assay showed inter- and intra-assay precision and accuracy values within ±15%. Matrix effects on different batches of serum, displayed accuracy within the required 10% correlation of variance (CV). Although the method showed unexpected recovery yields of 67-133%, the yields were stable. All analytes were stable at room temperature, +4˚C and -20˚C for at least 15 days; except for OXCBZ that must be analyzed straightaway or be kept at -20˚C until analysis. LLOQ (within ±20% accuracy and precision) was determined at 1.25 mg/L for Levetiracetam and Phenobarbital, 0.67 mg/L for Lamotrigine, 0.20 mg/L for CBZ-Diol, 1 mg/L for 10-OH-CBZ, 0.05 mg/L for CBZ-Epoxide, 0.10 mg/L for OXCBZ, 0.75 mg/L for Phenytoin and 0.40 mg/L for CBZ. All analytes were linear (within ±10% precision) at at least 300% of the highest calibration standard, with the exception of CBZ-Diol limited to 10 mg/L. In conclusion this method is suitable for routine analysis of the previously mentioned anti epileptic drugs and their metabolites.
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OrganisatieAvans Hogeschool
OpleidingChemische Technologie-Breda
AfdelingATGM Academie voor de technologie van Gezondheid en Milieu
PartnersAvans Hogeschool
Jaar2013
TypeBachelor
TaalNederlands

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