Development of total drug monitoring system and its application

本研究的目的是利用毛发分析来获得关于受试者过去药物使用的所有信息。这一概念被研究人员称为“总药物监测”。通过开发灵敏的高效液相或气相色谱方法，从头发样本中同时测定两种以上的药物。同时测定了精神分裂症患者头发中抗精神病药氟哌啶醇和氯丙嗪的浓度，并对影响头发药物浓度的因素进行了讨论。氧氟沙星是最广泛使用的抗菌剂氟喹诺酮类药物之一，在一根2毫米长的头发中进行了检测，并用作头发的时间标记。精神分裂症患者在氟哌啶醇治疗开始时只服用氧氟沙星一天。几到几个月后，从这些患者身上采集头发样本，研究氟哌啶醇、其代谢物(还原氟哌啶醇)和氧氟沙星沿单个毛干的轴向分布。头发中含有氧氟沙星的部分与最外层含有氟哌啶醇及其代谢物的部分吻合良好，表明氧氟沙星可以作为头发中的时间标记。用氧氟沙星作为时间标记物计算毛发生长率时，氟哌啶醇及其代谢物在毛干上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.