DETERMINATION OF ZOLPIDEM, A NEW SLEEP-INDUCING AGENT, AND ITS METABOLITES IN BIOLOGICAL-FLUIDS - PHARMACOKINETICS, DRUG-METABOLISM AND OVERDOSING INVESTIGATIONS IN HUMANS
DETERMINATION OF ZOLPIDEM, A NEW SLEEP-INDUCING AGENT, AND ITS METABOLITES IN BIOLOGICAL-FLUIDS - PHARMACOKINETICS, DRUG-METABOLISM AND OVERDOSING INVESTIGATIONS IN HUMANS
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DOI：
10.1016/0378-4347(92)80277-w
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发表时间：
1992-10-23
期刊：
影响因子：
--
通讯作者：
MORSELLI, PL
中科院分区：
文献类型：
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作者：
ASCALONE, V;FLAMINIO, L;MORSELLI, PL
为了测定新型睡眠诱导剂唑吡坦及其在人血浆和尿液中的代谢物，开发了三种适用于药代动力学、药物代谢和药物过量研究的方法。用于药代动力学和药物代谢研究的方法基于柱切换高效液相色谱；它们不需要任何样品操作，因为血浆或稀释的尿液被注入预柱，在那里进行净化和预浓缩。通过阀门切换将分析物转移至 C18 分析柱进行色谱分析。为了调查过量病例，仅使用尿液样本：方法简单，因为稀释的尿液可以直接注入分析柱（苯基型）。这使得可以对唑吡坦的主要尿代谢物进行鉴定和定量，而未改变的药物实际上是检测不到的。所有方法均采用荧光检测，具有高灵敏度和选择性。有必要使用一种能够测定代谢物的方法，即使这些代谢物显然没有药理学活性，因为在不同的病理生理人群中，唑吡坦的定性和定量代谢特征可能不同。根据这种情况的需要，为调查（意外或故意）用药过量病例而设计的方法简单而快速，并且相对于常用的精神药物具有良好的选择性。
For the determination of zolpidem, a new sleep inducer, and its metabolites in human plasma and urine, three methods were developed that are suitable for pharmacokinetics, drug metabolism and overdosing investigations. The methods used for pharmacokinetic and drug metabolism studies are based on column-switching high-performance liquid chromatography; they do not require any sample manipulation because the plasma or diluted urine is injected into a pre-column where clean-up and preconcentration take place. The analytes are transferred by valve-switching to the C18 analytical column for chromatography. To investigate overdose cases, urine samples only are used: the method is simple, because the diluted urine can be injected directly into the analytical column (phenyl type). This allows the identification and quantification of the principal urinary metabolite of zolpidem, the unchanged drug being practically undetectable. All the methods use fluorescence detection, which affords high sensitivity and selectivity. It is necessary to use a method capable of the determination of metabolites even if these are apparently pharmacologically inactive, because in different physiopathological populations the qualitative and quantitative metabolic profiles of zolpidem could be different. The method designed for the investigation of (accidental or deliberate) overdose cases is, as required on such occasions, simple and rapid, with good selectivity with respect to commonly prescribed psychotropic drugs.