RESUMEN
Intestinal oxalate absorption is an important part of oxalate metabolism influencing its urinary excretion and its measurement can be a valuable diagnostic tool in hyperoxaluric disorders. In this study, we use [(13)C(2)]oxalate absorption under standardized dietary conditions to assess intestinal oxalate absorption and its impact on urinary oxalate excretion. Tests were conducted in age-matched pediatric patients that included 60 with idiopathic calcium oxalate urolithiasis, 13 with primary hyperoxaluria, and 35 healthy children. In the idiopathic stone formers, median oxalate absorption was significantly higher than that in the controls or in patients with primary disease. From standardized values obtained in control patients, oxalate hyperabsorption was detected in 23 patients with idiopathic disease but not in any patients with primary hyperoxaluria; therefore, a significant correlation between intestinal absorption and urinary excretion was found only in those with the idiopathic disease. We have shown that increased intestinal oxalate absorption is an important risk factor of idiopathic calcium oxalate urolithiasis. In contrast, low intestinal oxalate absorption in patients with primary hyperoxaluria indicates that only foods with excessive oxalate content be restricted from their diet.
Asunto(s)
Oxalato de Calcio , Isótopos de Carbono/farmacocinética , Hiperoxaluria Primaria/metabolismo , Oxalatos/farmacocinética , Urolitiasis/metabolismo , Absorción , Adolescente , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: To compare quantitatively the effect of a low- and a high-oxalate vegetarian diet on intestinal oxalate absorption and urinary excretion. SUBJECTS AND METHODS: Eight healthy volunteers (three men and five women, mean age 28.6+/-6.3) were studied. Each volunteer performed the [(13)C(2)]oxalate absorption test thrice on a low-oxalate mixed diet, thrice on a low-oxalate vegetarian diet and thrice on a high-oxalate vegetarian diet. For each test, the volunteers had to adhere to an identical diet and collect their 24-h urines. In the morning of the second day, a capsule containing [(13)C(2)]oxalate was ingested. RESULTS: On the low-oxalate vegetarian diet, mean intestinal oxalate absorption and urinary oxalate excretion increased significantly to 15.8+/-2.9% (P=0.012) and 0.414+/-0.126 mmol/day (P=0.012), compared to the mixed diet. On the high-oxalate vegetarian diet, oxalate absorption (12.5+/-4.6%, P=0.161) and urinary excretion (0.340+/-0.077 mmol/day, P=0.093) did not change significantly, compared to the mixed diet. CONCLUSIONS: A vegetarian diet can only be recommended for calcium oxalate stone patients, if the diet (1) contains the recommended amounts of divalent cations such as calcium and its timing of ingestion to a meal rich in oxalate is considered and (2) excludes foodstuffs with a high content of nutritional factors, such as phytic acid, which are able to chelate calcium.
Asunto(s)
Dieta Vegetariana , Absorción Intestinal/efectos de los fármacos , Oxalatos/farmacología , Adolescente , Adulto , Anciano , Oxalato de Calcio/administración & dosificación , Oxalato de Calcio/metabolismo , Radioisótopos de Carbono , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxalatos/metabolismo , Oxalatos/orina , Adulto JovenRESUMEN
Primary hyperoxaluria is characterized by severe urolithiasis, nephrocalcinosis, and early renal failure. As treatment options are scarce, we aimed for a new therapeutic tool using colonic degradation of endogenous oxalate by Oxalobactor formigenes. Oxalobacter was orally administered for 4 weeks as frozen paste (IxOC-2) or as enteric-coated capsules (IxOC-3). Nine patients (five with normal renal function, one after liver-kidney transplantation, and three with renal failure) completed the IxOC-2 study. Seven patients (six with normal renal function and one after liver-kidney transplantation) completed the IxOC-3 study. Urinary oxalate or plasma oxalate in renal failure was determined at baseline, weekly during treatment and for a 2-week follow-up. The patients who showed >20% reduction both at the end of weeks 3 and 4 were considered as responders. Under IxOC-2, three out of five patients with normal renal function showed a 22-48% reduction of urinary oxalate. In addition, two renal failure patients experienced a significant reduction in plasma oxalate and amelioration of clinical symptoms. Under IxOC-3 treatment, four out of six patients with normal renal function responded with a reduction of urinary oxalate ranging from 38.5 to 92%. Although all subjects under IxOC-2 and 4 patients under IxOC-3 showed detectable levels of O. formigenes in stool during treatment, fecal recovery dropped directly at follow up, indicating only transient gastrointestinal-tract colonization. The preliminary data indicate that O. formigenes is safe, leads to a significant reduction of either urinary or plasma oxalate, and is a potential new treatment option for primary hyperoxaluria.
Asunto(s)
Hiperoxaluria Primaria/terapia , Oxalobacter formigenes , Administración Oral , Adolescente , Adulto , Cápsulas , Niño , Preescolar , Cromatografía de Gases , Creatinina/orina , Heces/microbiología , Femenino , Ionización de Llama , Estudios de Seguimiento , Humanos , Hiperoxaluria Primaria/sangre , Hiperoxaluria Primaria/clasificación , Hiperoxaluria Primaria/complicaciones , Hiperoxaluria Primaria/orina , Riñón/fisiología , Enfermedades Renales/complicaciones , Enfermedades Renales/diagnóstico por imagen , Fallo Renal Crónico/complicaciones , Pruebas de Función Renal , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Oxalatos/sangre , Oxalatos/orina , Oxalobacter formigenes/aislamiento & purificación , Factores de Tiempo , Resultado del Tratamiento , UltrasonografíaRESUMEN
Hyperoxaluria is the most important risk factor for a formation of calcium oxalate-urinary stones. Usually, the bulk of oxalate will be formed in the human body, but in many patients the oxalate from food plays the decisive role. Conventionally, in urine the endogenous oxalate can not be distinguished from food derived oxalate. We have developed a standardized oxalate-absorption test, applying a physiological dose (50 mg disodium salt of [13C2]oxalic acid) of labelled oxalate. The assay has been published. Now we report on the first extensive applications of this test in 86 volunteers and 135 patients from different groups with calcium oxalate stones or an increased risk of the formation of such stones. In one-third of the patients with calcium oxalate-urinary stones an oxalate hyperabsorption was diagnosed. For these patients, a dietetic stone prophylaxis and/or therapy is indicated.
Asunto(s)
Oxalato de Calcio/farmacocinética , Isótopos de Carbono , Cálculos Urinarios/diagnóstico , Absorción , Adolescente , Adulto , Anciano , Oxalato de Calcio/química , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
In up to one-third of patients with calcium oxalate stones, a hyperoxaluria can be detected. Hyperoxaluria can result from increased endogenous production, from excessive oxalate content of the food, or from intestinal hyperabsorption. For a causal therapy, it is important to discriminate between metabolic and hyperabsorptive hyperoxaluria. Our new 13C-oxalate test allows this differentiation. Under standardized conditions, 50 mg of disodium salt of [13C2]oxalic acid was applied. From the amount of labeled oxalate excreted in urine as measured by a gas chromatographic-mass spectrometric assay, the intestinal absorption was calculated. Seventy patients with recurrent calcium oxalate urolithiasis who had no signs of inflammatory bowel disease were tested. Their mean intestinal oxalate absorption was 9.2+/-5.1%. This was significantly higher than the mean absorption of 50 healthy volunteers (6.7+/-3.9%). There was no difference in oxalate absorption between male (n = 25) and female volunteers. Oxalate absorption correlated with the oxalate excretion in the 24-h urine (volunteers: r = 0.46, P < 0.01; patients: r = 0.62, P < 0.001). Oxalate hyperabsorption was defined as an absorption exceeding 10%. According to this definition, 34% of the patients had oxalate hyperabsorption; 20% of the volunteers showed a hyperabsorption, too. The 13C-oxalate absorption test allows reliable determination of intestinal oxalate absorption. Because of the use of a stable isotope, this test may be repeated as often as required. It will allow the control of therapeutic regimens and also help to unravel genetic influences in stone formation.
Asunto(s)
Oxalato de Calcio/metabolismo , Absorción Intestinal , Oxalatos/metabolismo , Cálculos Urinarios/metabolismo , Adolescente , Adulto , Isótopos de Carbono , Femenino , Humanos , Masculino , Persona de Mediana Edad , RecurrenciaRESUMEN
Tramadol, racemic 1-(3-methoxyphenyl)-2-(dimethylaminomethyl)cyclohexane-1-ol, is an effective analgesic drug. Metabolites of tramadol described so far originate from O- and N-demethylation and are excreted in urine directly or after conjugation. A further metabolite was found in human liver microsome incubations and in the urine of volunteers after ingestion of tramadol. To elucidate the structure of the new metabolite, seven deuterated isotopomers of tramadol have been synthesized and ingested by volunteers. The mass spectra of the metabolites derived showed (i) that it was a hydroxy metabolite, (ii) that the hydroxy group was not located on the aromatic ring, the side chain, or the positions 2 and 6 of the cyclohexane ring, (iii) that the hydroxy-group was introduced to one of the the positions 3, 4 or 5 of the cyclohexane ring. The hydroxy metabolite was formed preferentially from the (-)-enantiomer, (1S,2S)-tramadol.
Asunto(s)
Analgésicos Opioides/metabolismo , Tramadol/metabolismo , Analgésicos Opioides/química , Analgésicos Opioides/orina , Deuterio , Cromatografía de Gases y Espectrometría de Masas , Humanos , Hidroxilación , Masculino , Estructura Molecular , Estereoisomerismo , Tramadol/química , Tramadol/orinaRESUMEN
In order to assess the significance of the intestinal absorption of oxalate from food for the hyperoxaluria of the individual patient, an oxalate absorption test has been developed using doubly 13C-labelled oxalate and a gas chromatographic selected ion monitoring mass spectrometric assay. This test has been applied to volunteers and patients with urinary stones. The percentage of dose absorbed (range 1-48%) could be determined with a coefficient of variation of 15.2%. The assay to measure doubly 13C-labelled oxalate in the presence of unlabelled oxalate in urine, using the homologue malonic acid as internal standard, is described.
Asunto(s)
Cromatografía de Gases y Espectrometría de Masas/métodos , Absorción Intestinal , Oxalatos/farmacocinética , Isótopos de Carbono , Humanos , Oxalatos/orina , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Factores de Tiempo , Cálculos Urinarios/orinaRESUMEN
Abstract Tramadol, racemic 1-(3-methoxyphenyl)-2-(dimethylaminomethyl)cyclohexane-1-ol, is an effective analgesic drug. Metabolites of tramadol described so far originate from O- and N-demethylation and are excreted in urine directly or after conjugation. A further metabolite was found in human liver microsome incubations and in the urine of volunteers after ingestion of tramadol. To elucidate the structure of the new metabolite, seven deuterated isotopomers of tramadol have been synthesized and ingested by volunteers. The mass spectra of the metabolites derived showed (i) that it was a hydroxy metabolite, (ii) that the hydroxy group was not located on the aromatic ring, the side chain, or the positions 2 and 6 of the cyclohexane ring, (iii) that the hydroxy-group was introduced to one of the the positions 3, 4 or 5 of the cyclohexane ring. The hydroxy metabolite was formed preferentially from the (-)-enantiomer, (1S,2S)-tramadol.
RESUMEN
A sensitive assay for prenylamine and dideuteroprenylamine (racemic or pseudo-racemate) has been developed and used in human pharmacokinetic studies. Plasma levels of prenylamine could be measured up to 50 h after a single oral therapeutic dose. The extracted drug was derivatized with pentafluoropropionic anhydride in acetonitrile. The dried samples were reconstituted in decane; an aliquot was injected into a fused-silica capillary in a cooled on-column injector. The base peaks in the electron impact mass spectra of the compounds--derived by loss of a benzyl radical--at m/z 384, 386 and 390 were measured for prenylamine, (D2)-prenylamine and the internal standard hexahydroprenylamine, respectively. The sensitivity of this assay--limit of detection 0.2 ng ml-1 plasma with a signal-to-noise ratio of 5:1--allowed measurement of the kinetics of the racemate and of both stereoisomers for the first time. In man, the (+)-isomer was eliminated considerably faster than the (-)-prenylamine; the area under the plasma concentration time curve (AUC) of the (+)-isomer was only about 1/4 of the AUC of (-)-prenylamine.
Asunto(s)
Prenilamina/análisis , Disponibilidad Biológica , Cromatografía de Gases y Espectrometría de Masas , Humanos , Prenilamina/farmacocinética , EstereoisomerismoRESUMEN
A 19-year-old patient intending to commit suicide gave himself an intravenous injection of about 14 g methyliodide. The patient was admitted to our hospital in a state of somnolence and agitation followed by a cerebral convulsion and severe hypotension. The serum concentration of methyl iodide was measured by mass spectroscopy. In addition to an antidote therapy with acetylcysteine, haemoperfusion was performed followed by a remarkable decrease of the methyliodide concentration. The patient survived this severe intoxication and was discharged from the hospital after a week.
Asunto(s)
Hemoperfusión , Hidrocarburos Yodados/envenenamiento , Intoxicación/terapia , Intento de Suicidio , Acetilcisteína/uso terapéutico , Adulto , Antídotos/uso terapéutico , Humanos , Hidrocarburos Yodados/administración & dosificación , Inyecciones Intravenosas , Masculino , Intoxicación/tratamiento farmacológicoRESUMEN
Pharmacokinetics of racemic prenylamine were investigated in 6 healthy volunteers. Plasma levels were determined by gas chromatography/mass spectrometry. Concentration-time profiles were analyzed both by compartment-dependent and compartment-independent pharmacokinetic models. Terminal elimination half-life was 14.1 h (SD: 6.9 h). The apparent total clearance was 5.8 l/min. Mean residence time of racemic prenylamine was found to be 14.7 h (SD: 3.8 h). The relative bioavailability of prenylamine (Segontin 100) was 82.2% (SD: 9.9%) determined in six healthy volunteers. The volunteers received simultaneously the film tablet and 100 mg racemic dideuteroprenylamine as an aqueous solution of the lactate. This procedure is known to exclude intraindividual changes in absorption, first-pass metabolism or volume of distribution that might occur on sequential administration. The absolute bioavailability was estimated to be in the order of 15%. In a pilot study the pharmacokinetics of the enantiomers were investigated in 2 healthy volunteers. S-(+)-prenylamine was eliminated considerably faster from plasma than R-(-)-prenylamine suggesting a stereoselective metabolism. The AUC of the (+)-enantiomer was 20% of that of the R-(-)-prenylamine.
Asunto(s)
Prenilamina/farmacocinética , Adulto , Disponibilidad Biológica , Humanos , Indicadores y Reactivos , Masculino , EstereoisomerismoRESUMEN
1. The metabolism of eugenol (4-hydroxy-3-methoxy-allylbenzene) was investigated in male and female healthy volunteers. It was rapidly absorbed and metabolized after oral administration and was almost completely excreted in the urine within 24 h. Unmetabolized eugenol excreted in urine amounted to less than 0.1% of the dose. 2. The urine contained conjugates of eugenol and of nine metabolites. The structures of these metabolites, elucidated using g.l.c.-mass spectrometry, and by comparison with synthetic reference compounds, were identified as: eugenol, 4-hydroxy-3-methoxyphenyl-propane, cis- and trans-isoeugenol, 3-(4-hydroxy-3-methoxyphenyl)-propylene-1,2-oxide, 3-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol, and 3-(4-hydroxy-3-methoxyphenyl)-propionic acid. 3. The structures of the following metabolites were tentatively deduced from mass spectra only, as reference compounds were not available: 3-hydroxy-3-(4-hydroxy-3-methoxyphenyl)-allylbenzene, 3-(6?-mercapto-4-hydroxy-3-methoxyphenyl)-propane, and 2-hydroxy-3-(4-hydroxy-3-methoxyphenyl)-propionic acid. 4. The amounts of the individual metabolites excreted were determined by g.l.c. Some 95% of the dose was recovered in the urine, most of which (greater than 99%) consisted of phenolic conjugates; 50% of the conjugated metabolites were eugenol-glucuronide and sulphate. Other metabolic routes observed were the epoxide-diol pathway, synthesis of a thiophenol and of a substituted propionic acid, allylic oxidation, and migration of the double bond.
Asunto(s)
Eugenol/orina , Adulto , Femenino , Cromatografía de Gases y Espectrometría de Masas , Glucuronatos/orina , Humanos , Concentración de Iones de Hidrógeno , Masculino , Espectrometría de Masas , Estructura Molecular , Fenoles , Sulfatos/orinaRESUMEN
Following the oral administration of either chlorambucil/prednisolone or prednimustine to patients, the plasma levels of free chlorambucil and phenylacetic acid mustard, the beta-oxidation product of chlorambucil, were measured using a new high-performance liquid chromatographic (HPLC) assay. This assay permitted the simultaneous detection of the analyzed compounds with a lower limit of detection of 30 ng/ml. The pharmacokinetics of chlorambucil and phenylacetic acid mustard were found to be entirely different when prednimustine was administered as opposed to its components chlorambucil and prednisolone together. After the ingestion of the conjugate, the plasma concentration-time curves of chlorambucil and phenylacetic acid mustard showed a "delayed" pattern compared with those obtained after the administration of the components. The mean area under the concentration-time curves (AUCs) of prednimustine-derived chlorambucil and phenylacetic acid mustard were 25% and 40%, respectively, of the areas obtained after a stoichiometrically equivalent dose of chlorambucil. Free plasma prednimustine could not be detected at any time. This different pharmacokinetic behavior might offer an explanation for the superior therapeutic effects of prednimustine demonstrated by clinical studies.
Asunto(s)
Clorambucilo/análogos & derivados , Clorambucilo/farmacocinética , Prednimustina/farmacocinética , Clorambucilo/sangre , Cromatografía Líquida de Alta Presión/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Combinación de Medicamentos , Humanos , Compuestos de Mostaza Nitrogenada/sangre , Prednimustina/sangre , Prednisolona/sangre , Prednisolona/farmacocinética , Factores de TiempoRESUMEN
Gaschromatography--mass spectrometry (GC/MS) was used to determine plasma levels of oxcarbazepine (OCB) and its main metabolite in a newborn girl and her OCB-treated mother during the first five post partum days. At delivery the maternal and neonatal plasma concentrations were in the same range, indicating considerable placental transfer of both substances. In spite of ingestion of both substances via breast milk, there was no accumulation in the baby. On the fifth post partum day OCB and 10-hydroxy-carbazepine (10-OH-CB) levels in plasma in the newborn were only 12 and 7%, respectively, of the values found on the first day after delivery.
Asunto(s)
Anticonvulsivantes/farmacocinética , Carbamazepina/análogos & derivados , Recién Nacido/metabolismo , Adulto , Anticonvulsivantes/sangre , Anticonvulsivantes/uso terapéutico , Carbamazepina/sangre , Carbamazepina/farmacocinética , Carbamazepina/uso terapéutico , Femenino , Sangre Fetal/metabolismo , Semivida , Humanos , Leche Humana/metabolismo , OxcarbazepinaRESUMEN
A sensitive high-performance liquid chromatographic assay has been developed for the measurement of the alkylating cytostatic drug melphalan (4-[bis(2-chloroethyl)amino]-L-phenyl-alanine, or L-phenylalanine-mustard, L-PAM) and its two hydrolysis products, monohydroxy melphalan (MOH) and dihydroxy melphalan (DOH). A reversed-phase phenyl column and a mobile phase consisting of acetonitrile/citrate buffer made possible an isocratic separation and quantification. N,N-[bis(2-hydroxy-ethyl)]toluidine has been synthesized as an internal standard structurally related to DOH. A new, accurate "kinetic" calibration procedure enabled us to determine even the concentration of the unstable MOH. The lower limit of quantification was 30 ng/ml for L-PAM and 20 ng/ml for both DOH and MOH with fluorescence detection. The use of this method is illustrated by some pharmacokinetic data in systemic and locoregional melphalan therapy.
Asunto(s)
Melfalán/sangre , Calibración , Fenómenos Químicos , Química , Cromatografía Líquida de Alta Presión , Humanos , Hidrólisis , Melfalán/farmacocinética , Valor Predictivo de las Pruebas , Control de CalidadRESUMEN
Oxcarbazepine (OCB) cannot be measured undecomposed by gas chromatography, not even when injected into a cooled, inert fused-silica capillary column. The bis-trimethylsilyl derivatives of the enol of OCB and of its main metabolite, 10-hydroxy-carbazepine (10-OH-CB), and the tris-trimethylsilyl derivative of carbazepine-10,11-trans-diol (CB-trans-diol) can be obtained easily at room temperature and are well suited for gas chromatographic and gas chromatographic/mass spectrometric analysis. Thermal decomposition to the substituted iminostilbene derivatives occurs only to the extent of a few per cent under the conditions described. Two gas chromatographic/mass spectrometric assays have been developed: one for the simultaneous quantification of OCB and 10-OH-CB, the other for CB-trans-diol. Both assays use carbazepine-10,11-cis-diol as the internal standard. Using 0.5 ml of plasma, limits of detection of 0.1, 0.1 and 1 ng/ml were obtained for OCB, 10-OH-CB and CB-trans-diol, respectively. CB-trans-diol is also the main metabolite of carbamazepine in patients under maintenance therapy. The kinetics of 15N-labelled CB-trans-diol derived from a single dose of (15N)carbamazepine has been measured in plasma and urine of patients and volunteers receiving (15N)carbamazepine in several studies.
Asunto(s)
Anticonvulsivantes/sangre , Carbamazepina/análogos & derivados , Disponibilidad Biológica , Carbamazepina/sangre , Carbamazepina/metabolismo , Carbamazepina/uso terapéutico , Ensayos Clínicos como Asunto , Epilepsia/tratamiento farmacológico , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , OxcarbazepinaRESUMEN
The relative bioavailability was measured for the 150-, 300-, and 600-mg enteric coated Leptilan tablets (valproic acid, sodium salt) using a new method. Simultaneously an equimolar amount of a tetradeuterated valproic acid - di-(2,3-dideutero-n-propyl)-acetic acid - was given as an aqueous solution of the sodium salt. This methodology excludes effects on the two partial pharmacokinetics caused by time-dependent intraindividual variations of the metabolising capacity or other biochemical or physiological changes in the body of the volunteer. Therefore, this methodology gives already reliable data for bioavailability when using only small numbers of volunteers. The relative bioavailability of the enteric coated Leptilan tablets was 95.5 +/- 0.6%, 104.4 +/- 7.6%, and 100.7 +/- 2.4% (mean from experiments with 3 volunteers each) for the 150-, 300-, and 600-mg tablets respectively.
Asunto(s)
Ácido Valproico/metabolismo , Adulto , Disponibilidad Biológica , Deuterio , Femenino , Humanos , Cinética , Masculino , Comprimidos Recubiertos , Ácido Valproico/administración & dosificaciónRESUMEN
Carbamazepine (CBZ) labeled with 15N was used to investigate the mechanism of its pharmacokinetic interaction with the antiestrogenic steroid danazol during treatment of a patient with epilepsy. Danazol led to a pronounced inhibition of CBZ metabolism. During danazol coadministration, CBZ elimination half-life increased from a pretreatment value of 11 to 24.3 h. Carbamazepine plasma clearance decreased from 57.7 to 23.2 ml/h/kg. Kinetic analysis of the plasma concentration-time curves and urinary excretion of [15N]trans-CBZ-diol revealed that danazol inhibited the epoxide-trans-diol pathway of carbamazepine metabolism. Observations in five other female patients confirm that the steady-state plasma concentrations of UCBZ increase between 50 and 100% during coadministration of danazol.
Asunto(s)
Carbamazepina/metabolismo , Danazol/metabolismo , Pregnadienos/metabolismo , Adulto , Carbamazepina/sangre , Carbamazepina/orina , Carbón Orgánico , Danazol/sangre , Danazol/orina , Interacciones Farmacológicas , Femenino , Humanos , Cinética , Isótopos de NitrógenoRESUMEN
The new anti-epileptic drug oxcarbazepine is temperature-labile and decomposes under the conditions of gas chromatography, even when injected into a cooled, inert, fused-silica capillary column. In contrast, the trimethylsilyl derivative of oxcarbazepine is stable. The bis-trimethylsilyl derivatives of the enol of oxcarbazepine and of its active metabolite, 10-hydroxycarbazepine, and the tris-trimethylsilyl derivative of carbazepine-10,11-trans-diol can be synthesized easily at room temperature. Using the readily available carbamazepine as internal standard, a simple gas chromatographic assay was developed for the simultaneous routine measurement of these three compounds at therapeutic levels. This assay is ten times more sensitive to oxcarbazepine than the previously described high-performance liquid chromatographic assays. It involves a single-step solvent extraction, uses a fused-silica capillary column and a flame ionization detector. On processing 0.5 ml of plasma, limits of detection of 10 ng/ml were obtained for oxcarbazepine and 10-hydroxycarbazepine and a limit of detection of 25 ng/ml for carbazepine-10,11-trans-diol.