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Determination of midazolam in rabbit plasma by GC and LC following nasal and ocular administration
Author(s) -
Jaček Martin,
Matějčková Jana,
Málek Jiří,
Hess Ladislav,
Samcová Eva
Publication year - 2013
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.201300401
Subject(s) - chromatography , chemistry , detection limit , extraction (chemistry) , high performance liquid chromatography , chloride , analyte , midazolam , nitrogen , phosphorus , pharmacology , medicine , organic chemistry , sedation
GC with nitrogen phosphorus detection and HPLC with UV detection were used to determine midazolam ( MDZ ) levels in rabbit plasma following ocular and nasal administration. For GC with nitrogen phosphorus detection, the analyte was extracted from the plasma using a three‐step liquid–liquid extraction including extraction with an isopropanol/butyl chloride mixture in an alkaline solution, followed by extractions with 1 M HCl, and finally with an alkaline solution of butyl chloride. The recovery of MDZ was dependent on the sample alkalization time prior to the final extraction. The procedure increased the recovery of MDZ up to 99.6%. Improved sample preparation led to a significant increase in the sensitivity of the determination by GC with nitrogen phosphorus detection. The achieved detection limit was 0.34 ng/mL, which is ten times lower than that obtained using HPLC with UV detection. The small plasma volume was another advantage of the GC with nitrogen phosphorus detection method (200 μL per assay). Both administration routes of the anesthetic (nasal and ocular) resulted in comparable plasma MDZ levels. Kinetic simulation of the MDZ plasma was performed for both administration routes.