Screening for hydroxylation and acetylation polymorphisms in man via simultaneous analysis of urinary metabolites of mephenytoin, dextromethorphan and caffeine by capillary electrophoretic procedures.

Phenotypes for hydroxylation can be predicted by using mephenytoin and dextromethorphan as substrates, whereas phenotypes for acetylation can be determined with caffeine as probe drug. After single-dose administration of one of these drugs, of two of them simultaneously, or of the three drugs together, the major urinary metabolites (4-hydroxymephenytoin; dextrorphan, 3-methoxymorphinan, 3-hydroxymorphinan; 5-acetylamino-6-amino-3-methyluracil as decomposition product of 5-acetylamino-6-formylamino-3-methyluracil, 1-methylxanthine, respectively) of these substrates were analyzed by capillary electrophoretic techniques. No sample pretreatment other than enzymatic hydrolysis of the conjugated compounds was applied. Assays based on micellar electrokinetic capillary chromatography are shown to allow simultaneous and unambiguous phenotyping with mephenytoin and dextromethorphan or mephenytoin and caffeine. Simultaneous screening for all three polymorphisms with a single injection of a hydrolyzed urine is shown to be possible via use of multiwavelength absorption detection only. Phenotypes determined by electrokinetic capillary techniques are shown to agree with those obtained by analysis with customary assays based on high-performance liquid chromatography.

Assessment of automated capillary electrophoresis for therapeutic and diagnostic drug monitoring: determination of bupivacaine in drain fluid and antipyrine in plasma.

In an effort to evaluate the use of electrokinetic capillary technology for therapeutic and diagnostic drug monitoring, samples were analysed batchwise with an automated, high-throughput capillary electrophoretic instrument coupled to an inexpensive PC data acquisition and evaluation system. Examples studied included the capillary electrophoretic (HPCE) determination of bupivacaine in drain fluid collected after pulmonary surgery and the micellar electrokinetic capillary chromatographic (MECC) determination of antipyrine in human plasma. Analyses for antipyrine could be accomplished without any sample pretreatment whereas bupivacaine required extraction prior to analysis. Antipyrine determination was effected through external calibration using either peak areas, relative peak areas or peak heights. The intraday and interday reproducibilities (n = 15) of the evaluated concentrations were 1.5-3% and 5-6%, respectively. For bupivacaine, determination based on internal and external calibration employing peak areas and peak heights was investigated. The intraday and interday reproducibilities (n = 5) of bupivacaine concentrations were about 1% and 2%, respectively, for internal calibration and both about 5% for external calibration. The electrokinetic capillary data compared well with data obtained by gas chromatography (bupivacaine) and high-performance liquid chromatography (antipyrine).

[Aplastic anemia in carbamazepine therapy]. / Aplastische Anämie bei Carbamazepintherapie.

We report a case of carbamazepine-induced aplastic anemia. After an initial treatment period of 10 days (600 mg/day), moderate, persisting pancytopenia was observed. Three years later, carbamazepine treatment was resumed at 400 mg/day for 120 days. Subsequently, more severe, irreversible pancytopenia due to bone marrow aplasia was diagnosed. History, course, bone marrow findings and the extensive, negative work-up for other causes of aplastic anemia strongly indicate that carbamazepine was etiologically responsible. Aplastic anemia secondary to carbamazepine treatment is rarely reported. Information on the dose and time of exposure are only available from anecdotal case reports. Based on a literature survey we analyze the risk of this potentially lethal hematological side-effect and make recommendations for routine blood checks.