High-performance Liquid Chromatographic Method for the Simultaneous Quantification of Three Benzodiazepines in Plasma

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  • HISHIDA HIROSHI
    Department of Pharmacy, and Clinical Encephalographic Center, Nagoya National Hospital
  • TAKEDA SHINYA
    Department of Pharmacy, and Clinical Encephalographic Center, Nagoya National Hospital
  • YONESHIMA RYUICHI
    Department of Pharmacy, and Clinical Encephalographic Center, Nagoya National Hospital
  • TAKEDA AKIO
    Department of Clinical Laboratory, Nagoya National Hospital

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  • 高速液体クロマトグラフィーによる三種ベンゾジアゼピン誘導体の同時測定

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Abstract

Many benzodiazepines have valuable anticonvulsant properties. The regular monitoring of plasma concentration of benzodiazepine derivatives during treatment with the drug appears not only useful but necessary, because of the narrow therapeutic iange and risk of increased occurrence of seizure in cases of overdosage.<BR>We studied a high-performance liquid chromatographic method for the simultaneous quantification of 3 benzodiazepine derivatives in plasma. After a single extraction of the drugs from alkaline plasma, nitrazepam, clonazepam and diazepam can be resolved and quantified by using an ODS reversed phase column with 2 volumes of acetnitrile and 5 volumes of 1% triethylamine-phosphoric acid solution (pH 3.0) as mobile phase. By adding triethylamine to mobile phase, retention time can be shortened for diazepam and the other benzodiazepines can also be separated completely. The eluted drugs were detected by their absorption at 254 nm. With this method, it is possible to quantify as little as 6 ng/ml foe nitrazepam and clonazepam, 18ng/ml for diazepam with 1ml plasma samples. Complete chromatographic resolution of the benzodiazepines resulted, permitting quantification of all being done within 30 min. The standard curves showed good linearity with ranges 6 to 400ng/ml for nitrazepam and clonazepam, and 18 to 1000 ng/ml for diazepam.<BR>The day-to-day precision, established by 10 replicate analyses, yielded CVs of 4.5 to 5.0%. Analytical recovery of each drugs added toplasma was complete (95 to 99%). The most common antiepileptics and plasma components did not intefere with the analysis.

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