Prolonged excretion of 7-aminoclonazepam in urine after repeated ingestion of clonazepam: a case report.

Urinary analyses of the metabolite 7-aminoclonazepam (7-AC) can be helpful in monitoring drug abuse and in the context of suspected drug-facilitated sexual assaults (DFSA). Only two studies have reported detection times of 7-AC in urine after a single dose of clonazepam, and no previous studies have reported detection times after repeated ingestions of clonazepam. This report describes along detection time of 7-AC in urine in the case of a 28-year-old woman with a two year history of daily drug abuse of heroin and clonazepam, who was admitted to a detoxification unit. Urinary samples were delivered every morning for 9 days. Screening analysis in urine was performed by immunoassay, and confirmation analysis by LC-MS/MS. 7-AC was detected for 9 days, and the concentration at day 9 was still high (97 ng/ml), compared to previously reported data. These results indicate that after repeated ingestions of clonazepam, 7-AC can possibly be detected for about 2-3 weeks after cessation, applying cut-off levels commonly used in drug testing programs and DFSA cases.

Structural and functional characterization of vitronectin-derived RGD-containing peptides from human hemofiltrate.

Bioactive peptides derived from the adhesive plasma protein vitronectin are present at submicromolar concentrations in human hemofiltrate of patients with renal diseases and were isolated by a combination of high-efficiency chromatographic steps. The structural and functional properties of these peptides were characterized. Sequencing and mass spectrometry revealed the existence of peptide isoforms (5-6 kDa) which corresponded to the N-terminus (residues 1 to 44-50) of vitronectin. The isolated peptides bound directly to plasminogen-activator inhibitor-1 (PAI-1) and were effective competitors of the interaction of PAI-1 with isolated intact vitronectin or extracellular matrix. These functional properties were indistinguishable from the binding properties of a recombinant fusion protein containing residues 1-52 of vitronectin linked to a portion of glutathione S-transferase, expressed in Escherichia coli. Peptides containing the RGD sequence of vitronectin competed for vitronectin binding to the alpha v beta 3 integrin. No indication for direct growth-factor binding was noted, whereas natural peptides were found associated with PAI-1 as the major binding protein in plasma. These data demonstrate that functionally active vitronectin-derived peptides are released by unknown protease(s) from the mature protein and that these peptides are identical, in terms of activity, to recombinant vitronectin fragments. These natural peptides may interact with active PAI-1 in plasma or at extravascular sites and thereby interfere with established biological functions of intact vitronectin.

[Gas-liquid chromatographic assay of a new antineoplastic agent, 1,3,3,5,5-pentakis-(azaridino)lambda 6-2,4,6,3 lambda 5, 5 lambda 5-thiatriazadiphosphorine-1-oxide. Application to pharmacokinetic studies]. / Dosage par chromatographie gaz-liquide d'un nouvel antitumoral, 1,3,3,5,5-pentakis-(azaridino)-lambda 6,2,4,6,3 lambda 5,5 lambda 5-thiatriazadiphosphorine-1-oxyde. Applications aux études pharmacocinétiques.

A method for the assay of 1,3,3,5,5-pentakis-(azaridino)-lambda 6,2,4,6,3 lambda 5,5 lambda 5-thiatriazadiphosphorine-1-oxide (SOAz), a new anticancer drug of which the clinical trials are in progress, is described. This method is based on capillary gas chromatography using a thermionic detector. The lower detection limit was 100 pg per injection and a coefficient of variation smaller than 5% could be obtained when parathion was used as external standard. The method is suitable for biological samples and therefore has been proposed for clinical pharmacokinetic studies as well as for the determination of patterns of SOAz distribution in several organs of the mouse. A preliminary clinical study showed that the serum decay curves of SOAz could be fitted to an open two-compartment model for drug disappearance.