Lappenberg-Pelzer M
Department of Clinical Toxicology and Pharmacology, Berliner Betrieb für Zentrale Gesundheitliche Aufgaben, Berlin, Germany.
J Anal Toxicol. 1998 May-Jun;22(3):215-9. doi: 10.1093/jat/22.3.215.
In six cases of suspected opipramol overdose, commercially available immunoassays for tricyclic antidepressants (TCA) EMIT tox serum Assay and ADxR serum TCA Assay indicated arbitrarily high or toxic TCA concentrations. However, opipramol concentrations determined by high-performance liquid chromatography (HPLC) analysis were in the high-normal or low-toxic range. This finding prompted us to study opipramol metabolism by mass spectral techniques and to determine the cross-reactivity of opipramol and its metabolites in immunoassays. Three previously unknown metabolites (I, II, V) included an oxidation product of the hydroxyethyl moiety to an acetic acid group at the piperazine side chain (1), a decarboxylation product of the latter metabolite (II), and opipramol-N-oxide (V). In addition, two previously reported metabolites were identified, which included a deshydroxyethyl metabolite (III) and dibenzazepine (IV). One of the major metabolites of opipramol is the acetic acid metabolite (I), which may exceed the opipramol plasma concentration immensely and contribute to an arbitrarily high concentration in commercially available immunoassays. The cross-reactivities of the metabolite (I) were determined to be 64 and 66% with EMIT and ADx, respectively.
在6例怀疑奥匹哌醇过量的病例中，市售的三环类抗抑郁药（TCA）免疫分析法EMIT tox血清检测法和ADxR血清TCA检测法显示三环类抗抑郁药浓度异常高或呈中毒水平。然而，通过高效液相色谱（HPLC）分析测定的奥匹哌醇浓度处于高正常范围或低中毒范围。这一发现促使我们通过质谱技术研究奥匹哌醇的代谢情况，并确定奥匹哌醇及其代谢产物在免疫分析中的交叉反应性。三种先前未知的代谢产物（I、II、V）包括哌嗪侧链上羟乙基部分氧化为乙酸基团的产物（I）、后一代谢产物（II）的脱羧产物以及奥匹哌醇 - N - 氧化物（V）。此外，还鉴定出两种先前报道过的代谢产物，包括去羟乙基代谢产物（III）和二苯并氮杂䓬（IV）。奥匹哌醇的主要代谢产物之一是乙酸代谢产物（I），其在血浆中的浓度可能大大超过奥匹哌醇，并导致市售免疫分析中出现异常高的浓度。已确定代谢产物（I）与EMIT和ADx的交叉反应性分别为64%和66%。
