Methotrimeprazine-induced corneal deposits and cataract revealed by urine drug profiling test.

Two schizophrenic patients who had been taking medication for a long period presented with visual disturbance of 6-month duration. Slit-lamp examination revealed fine, discrete, and brownish deposits on the posterior cornea. In addition, bilateral star-shaped anterior subcapsular lens opacities, which were dense, dust-like granular deposits, were noted. Although we strongly suspected that the patient might have taken one of the drugs of the phenothiazine family, we were unable to obtain a history of medications other than haloperidol and risperidone, which were taken for 3 yr. We performed a drug profiling test using urine samples and detected methotrimeprazine. The patient underwent surgery for anterior subcapsular lens opacities. Visual acuity improved in both eyes, but the corneal deposits remained. We report an unusual case of methotrimeprazine-induced corneal deposits and cataract in a patient with psychosis, identified by using the urine drug profiling test.

Metabolism of levomepromazine in man.

The phenothiazine drug, levomepromazine (LM), is used in the treatment of psychiatric disorders and as an analgesic. A single 50 or 100 mg dose of LM was given to healthy male volunteers, and urine samples were collected for 24 h. The urine was treated with beta-glucuronidase, purified by solid-phase extraction, and analyzed on a GC-MS system for identification of LM metabolites. Mass spectra suggesting 14 different LM metabolites were obtained from the samples. Our of these, 13 spectra could be ascribed to specific metabolites, 5 of which have not previously been identified. All these 5 metabolites were hydroxylated at the phenothiazine nucleus. Although the applied method did not determine the positions of hydroxyl groups on phenothiazine nuclei. 3 of the 5 metabolites were identified as O-desmethyl 3-hydroxy LM, O-desmethyl 7-hydroxy LM, and N,O-didesmethyl 7-hydroxy LM, based on their chromatographic properties. In addition two metabolites, one being hydroxylated on the phenothiazine nucleus, and one being O-demethylated and hydroxylated on the nucleus, were found. It is suggested that these were 8-hydroxy LM and O-desmethyl 8-hydroxy LM. The concentrations of 3-hydroxy LM (free+conjugated) appeared to be much higher than the concentrations of any other metabolite in the samples.

High-performance liquid chromatographic determination of levomepromazine (methotrimeprazine) and its main metabolites in serum and urine.

A new analytical method has been developed for simultaneous quantitation of levomepromazine and its five main metabolites in serum and urine. The method uses C-2 bonded phase extraction and reversed-phase high-performance liquid chromatography, based on ion-pair formation with dodecyl sulfate. The detection limits were 15 nM for levomepromazine and N-desmethyl levomepromazine, 28 nM for levomepromazine sulfoxide, and 56 nM for 3-hydroxylevomepromazine. 7-hydroxylevomepromazine, and O-desmethyllevomepromazine in serum, and lower in urine. The method was applied to measure steady-state serum and urine concentrations of levomepromazine and metabolites in five psychiatric patients. The concentrations of levomepromazine sulfoxide and N-desmethyllevomepromazine were generally higher than the concentrations of levomepromazine. The hydroxylated and O-demethylated metabolites were also found in higher concentrations than levomepromazine, but mainly as conjugates.

Simultaneous determination of chlorpromazine and levomepromazine in human plasma and urine by high-performance liquid chromatography using electrochemical detection.

A rapid, selective and sensitive method for the simultaneous determination of chlorpromazine and levomepromazine in human plasma and urine has been developed using high-performance liquid chromatography with electrochemical detection. The unchanged drugs and internal standard extracted from plasma and urine were separated by reversed-phase high-performance liquid chromatography. The influence of acetonitrile concentration and of the pH of the mobile phase were investigated. The detection limits were 100 pg for chlorpromazine and for levomepromazine. In comparison with three other detection systems this was found to be the most sensitive method. This method was successfully applied to the simultaneous determination of chlorpromazine and levomepromazine in human plasma and urine for pharmacokinetic studies.

Identification of nonpolar methotrimeprazine metabolites in plasma and urine by GLC-mass spectrometry.

Two metabolites of methotrimeprazine, the sulfoxide and the demethylated analog, were identified in extracts from patient plasma by combined GLC-mass spectrometry. Methotrimeprazine and its sulfoxide had similar mass spectra but different GLC retention times. In addition to the metabolites found in plasma, two other metabolites, the didesmethyl analog and the monodesmethyl sulfoxide, were identified in a urine extract.