Development of total drug monitoring system and its application

本研究的目的是利用头发分析来获得受试者过去使用药物的所有信息。这个概念被研究者称为“全药物监测”。采用高效液相色谱法（HPLC）或GLC法同时测定头发样品中两种以上的药物。本文从精神分裂症患者的头发中同时测定抗精神病药氟哌啶醇和氯丙嗪，并讨论了影响头发中药物浓度的因素。氧氟沙星是使用最广泛的抗菌氟喹诺酮类药物之一，研究人员在一根2毫米长的头发中测量氧氟沙星的含量，并将其用作头发中的时间标记。在精神分裂症患者中，氟哌啶醇治疗开始时仅给予氧氟沙星一天。几至几个月后，从这些患者身上获得头发样本，并沿单个发干调查氟哌啶醇及其代谢物（还原氟哌啶醇）和氧氟沙星的轴向分布。含有氧氟沙星的头发部分与含有氟哌啶醇及其代谢物的最外层部分吻合良好，表明氧氟沙星可以作为头发的时间标记物。以氧氟沙星为时间标记计算毛发生长速率时，氟哌啶醇及其代谢物沿毛干的分布可以很好地推断氟哌啶醇的剂量和持续时间。

The aim of the present study was to utilize hair analysis for obtaining all informations about the past drug uses in a subject. This concept is termed as "total drug monitoring" by the investigator.From hair samples more than two drugs were simultaneously determined by developing a sensitive HPLC or GLC method. Antipsychotic haloperidol and chlorpromazine were simultaneously measured in a single hair sampled from schizophrenic patients and the factor determining the drug concentration in hair was discussed. Ofloxacin, one of the most widely used antimicrobial fluoroquinolone, was measured in a 2-mm long piece of hair andused as a time-marker in hair.In schizophrenic patients ofloxacin was administered only for one day at the beginning of the therapy with haloperidol. A few to several months later hair samples were obtained from those patients and the axial distribution of haloperidol, its metabolite (reduced haloperidol) and ofloxacin was investigated along a single hair shaft. The hair portion containing ofloxacin coincided well with the outermost portion containing haloperidol and its metabolite, showing that ofloxacin can act as a time-marker in hair. When the hair growth rate was calculated by using ofloxacin as a time-marker, the dose and duration of haloperidol could be well deduced from the distribution of haloperidol and its metabolite along the hair shaft.