Assay method for the carboxylic acid metabolite of clopidogrel in human plasma by gas chromatography-mass spectrometry.

This paper describes a GC-MS method for the analysis of the carboxylic acid metabolite (SR26334, II) of methyl (+)-(S)-alpha-(o-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5( 4H)-acetate hydrogensulfate (clopidogrel, SR 25990, I) in plasma and serum. The analytical procedure involves a robotic liquid-liquid extraction with diethyl ether followed by a solid-liquid extraction on C18 cartridges. The derivatization process was performed using n-ethyl diisopropylethylamine and alpha-bromo-2,3,4,5,6-pentafluoro toluene. A structural analogue (III) of II, was used as internal standard. The 1/X2; weighted calibration curve obtained in the range 5-250 ng/ml was well described by a quadratic equation. The extraction efficiency was better than 48% over the range studied; for the internal standard it averaged 51% at 50 ng/ml. Precision ranged from 3.6 to 15.8%, and accuracy was between 92 and 114%. Dilution has no influence on the performance of the method which could then be used to quantitate plasma samples containing up to 25000 ng/ml. The limit of quantification was 5 ng/ml. The method validation results indicate that the performance characteristics of the method fulfilled the requirements for assay methods for use in pharmacokinetic studies.

[Effort-induced atrioventricular block. Apropos of 62 cases]. / Blocs auriculo-ventriculaires d'effort. A propos de 62 cas.

Based on a retrospective study, we report the clinical and electrophysiological characteristics of 62 cases of effort-induced atrio-ventricular block (AVB). The diagnosis of effort-induced AVB was established by stress test and/or Holter ECG. This series consisted of 18 women and 44 men with a mean age of 64 +/- 13 years. AVB presented in the form of poor adaptation to effort in 41 patients (66%), fainting and/or presyncope suggestive of Stokes-Adams attacks in 20 patients (32%), associated with poor adaptation to effort, except in 5 patients. 48 patients (77%) did not have any underlying heart disease. The ECG was normal in 25 patients (40%) or abnormal, demonstrating a 1st degree AVB and/or an intraventricular conduction disorder. On electrophysiological investigation, the AVB was type II (Mobitz II) in 48 patients (77%), generally 2/1. The block was infranodal, either in or below the His bundle, in 56 patients (90%). When it was situated above the His bundle, it was organic and degenerative, situated at the AV node, at the node-His junction, or even proximally in the His bundle. Effort-induced AVB implies DDD atrioventricular stimulation. The presence of this anomaly should be investigated in patients with poor adaptation to effort, but also when the clinical picture is dominated by Stokes-Adam attacks.

[Tilt test in the etiological diagnosis of syncope unexplained by electrophysiological study]. / Apport du test d'inclinaison dans le diagnostic étiologique des syncopes inexpliquées après exploration électrophysiologique.

In order to determine the role of tilt testing in the aetiological diagnosis of syncope unexplained by electrophysiological investigation, the authors retrospectively studied the results of this test in 275 patients with a mean age of 64 +/- 16 years. These 275 patients were divided into two groups: group I: 43 patients with a mean age of 50 +/- 19 years presenting with vagal syncopes, group II: 232 patients with unexplained syncope, probably vagal: group IIa (120 patients, mean age: 67 +/- 15 years), sudden syncope: group IIb (112 patients, mean age: 67 +/- 13 years). The electrophysiological investigation was inconclusive in every case. In group II, 50% of tilt tests were positive (19% under basal conditions, 31% after isoproterenol), with 61% of positive tests in group IIa, including 31% on the basal test, and 38% of positive tests in group IIb, including 11% on the basal test. In group I, 84% of tests were positive (33% on the basal test, 51% after isoproterenol), indicating a sensitivity of the test of 84%. In 96 patients with a doubtful electrophysiological investigation, the tilt test was positive in 70% of cases, allowing specific treatment or a pacemaker to be avoided in the majority of cases. 84% of vasovagal syncopes were therefore confirmed by tilt testing; 50% of syncopes unexplained by electrophysiological investigation were demonstrated to be of vasovagal origin. The author emphasize the value of tilt testing in certain discordant situations in which the clinical context is disturbing and/or electrophysiological investigation is not completely reassuring.

[Myocardial infarction, late fibrinolysis and resolving cerebral embolism]. / Infarctus du myocarde, fibrinolyse tardive et embolie cérébrale régressive.

The authors report a case of a cerebral embolism, with a rapidly resolving course, during late fibrinolysis using tissue plasminogen activator in a patient with a posterolateral myocardial infarction. A review of the literature is used as basis for considering the effects of fibrinolytic treatment on left intraventricular thrombi during the acute phase of myocardial infarction. The risk of systemic embolism during such treatment is stressed.