Isolation and identification of a new impurity in lorazepam substance.

A new impurity in lorazepam (1) was UV-detected during the HPLC-analysis of compound 1, batch scale. After the preparative chromatography on silica gel this impurity was isolated. According to IR, NMR, MS and elemental analysis the new impurity was identified as 7-chloro-5-(2-chlorophenyl)-2,3- dioxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine (2).

Biotransformations and plasma-level curves of chiral 1,4-benzodiazepine-2-ones.

Biotransformations of chiral 1,4-benzodiazepine-2-ones, (S)- and (R)-1 (7-chloro-1,3-dihydro-3 (S and R)-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one) in untreated and phenobarbital-pretreated rats were investigated. In urine, a 4'-oxygenated metabolite (compound 2) was identified as the biotransformation product from both enantiomers, (S)-2 being present in much higher amounts than (R)-2. Unchanged parent compounds were not found in urine. In plasma, 3'- and 4'-oxygenated metabolites were identified after administration of (S)-1 and (R)-1, respectively. The metabolite possessing an R-configuration was present in much lower amounts. The maximum concentrations of (R)-1 in plasma, following a single dose, was about 6 time as high as the maximum plasma concentration of (S)-1. Faster biotransformation and elimination of (S)-1 is assumed to be the explanation of these findings.

Outpatient use of systemic antibiotics in croatia.

OBJECTIVE: The aim was to estimate the outpatient utilization of antibacterials for systemic use in Zagreb, Croatia, and to define the antibiotic utilization characteristics and consequences. METHOD: Using the WHO ATC/DDD methodology, the number of defined daily doses per 1000 inhabitants per day (DDDs/TID) was calculated for each individual antibiotic and ATC system levels were calculated from data collected on the number and size of packages prescribed and dispensed from pharmacies. The Drug Utilization 90% (DU90%) method was used to evaluate the quality of drug prescribing. RESULTS: The total utilization of antibiotics was found to be extremely high, 55.0 DDDs/TID. The leading antibiotic was amoxicillin + clavulanic acid with 14.7 DDDs/TID. Penicillins accounted for the highest utilization (46.3%) expressed in DDDs/TID (25.4), followed by cephalosporins and macrolides 25 and 12.5% of utilization, respectively expressed in DDDs/TID), tetracyclines, quinolones, aminoglycosides and other agents. Nine of 27 antibiotics fell within the DU90% segment. The cost/DDD foldrugs within DU90% segment was 1.2 EUR, for drugs beyond DU90% segment was 1.4 EUR, and the average was 1.2 EUR. CONCLUSION: Irrational prescribing and preference to more expensive drugs have been reported in Zagreb. Therefore, the risk of resistance of microorganisms to beta-lactamase antibiotics, macrolides and quinolones could be expected. Prescribing patterns should be changed by introducing national guidelines on rational antibiotic prescribing, monitoring and evaluation of their implementation. Additional continuing education of physicians and pharmacists from independent sources should be organized and proper education should be provided to patients.