tailieunhanh - Drugs and Poisons in Humans - A Handbook of Practical Analysis (Part 27)

Introduction: Phenothiazine drugs, including chlorpromazine and levomepromazine, have been being widely used as neuroleptics (major tranquilizers), antiparkinsonian drugs and antihistaminics for a long time [1]. Table shows chemical structures of representative phenothiazines. These drugs show blocking action on D2 receptors of dopaminergic neurons; there is close relationship between the receptor blocking and tranquilizing actions. The dopamine D2 receptor-blocking actions provoke extrapyramidal symptoms, such as muscular stiffness, tremor and ptyalism. Orthostatic hypotension, arrythmia and icterus are occasionally found after administration of phenothiazines as side effects. The number of phenothiazine poisoning cases is relatively small, as compared with the extensive. | Phenothiazines by Akira Ishii and Yoshinao Katsumata Introduction Phenothiazine drugs including chlorpromazine and levomepromazine have been being widely used as neuroleptics major tranquilizers antiparkinsonian drugs and antihistaminics for a long time 1 . Table shows chemical structures of representative phenothiazines. These drugs show blocking action on D2 receptors of dopaminergic neurons there is close relationship between the receptor blocking and tranquilizing actions. The dopamine D2 receptor-blocking actions provoke extrapyramidal symptoms such as muscular stiffness tremor and ptyalism. Orthostatic hypotension arrythmia and icterus are occasionally found after administration of phenothiazines as side effects. The number of phenothiazine poisoning cases is relatively small as compared with the extensive use of this group of drugs 2 . However until now many phenothiazine poisoning cases including fatal ones 3 4 were reported. Phenothiazines were analyzed by various methods such as GC GC MS HPLC and LC MS. The methods by GC and GC MS are relatively simple but most of the methods reported used packed columns or wide-bore capillary columns 5 6 which did not give high sensitivity. Hattori et al. 7 reported a highly sensitive method for detecting phenothiazine in body fluids using GC-surface ionization detection SID a. Although the SID detector has an advantage in that each compound having a tertiary amino group can be analyzed with high sensitivity and specificity it is not a detector commonly available. In this chapter the methods of qualitative and quantitative analysis of phenothiazines in human body fluids using useful GC MS and LC MS are presented. GC MS analysis Reagents and their preparation i. Reagents Chlorpromazine triflupromazine promethazine and t hioridazine can be purchased from Sigma St. Louis MO USA . Pure powder of levomepromazine was donated by Mitsubishi Welpharma Osaka Japan. Other common chemicals were of the highest purity .