Micronomicin sulfate

An ultraviolet spectrophotometric method for determination of micromonicin (MCR) was developed by the reaction of MCR with o-pathaldehyde (OPA) and obtained a derivative absorbing ultraviolet in special wave length. The comparison was made between this method and high performance liquid chromatography (HPLC). The results indicate that the method is simple, rapid, precise and reproducible.

In recent years, aminoglycoside agents as well as beta-lactam antibiotics have been increasingly used with increased incidence of opportunistic infection caused mainly by Gram-negative bacteria. Therefore, we administered micronomicin sulfate (MCR), reportedly lower in nephrotoxicity, at doses of 60 and 120 mg by intravenous drip infusion for 1 and 2 hours to healthy male volunteers and determined the blood level and the urinary recovery rate. The peak of blood level after 1 hour infusion of MCR was 7.3 micrograms/ml in the 60 mg group and 9.5 micrograms/ml in the 120 mg group. T 1/2 (beta) was 3.34 and 2.48 hours respectively. The peak of blood level after 2 hours infusion of MCR was 5.7 micrograms/ml in the 60 mg group and 8.7 micrograms/ml in the 120 mg group. T 1/2 (beta) was 3.36 and 3.71 hours respectively. In the 120 mg group, the urinary recovery rate for the first 24 hours was 53.5% after 1 hour infusion and 60.9% after 2 hours infusion.

The neuromuscular blocking actions of sisomicin sulfate (SISO), micronomicin sulfate (MCR) and d-tubocurarine (dTc) were studied in 20 rabbits anesthetized with halothane. The i.v. administration of SISO 20-40 mg/kg, MCR 40-80 mg/kg or dTc 0.1-0.3 mg/kg resulted in dose-dependent decreases in twitch tension. The ED50s for SISO, MCR and dTc were 23.5, 58.2 and 0.2 mg/kg, respectively. SISO- and MCR-induced neuromuscular blockade was partially antagonized by neostigmine or by calcium.

This paper describes the separation of the main component micronomicin from its related substances using a new established liquid chromatographic method with pulsed electrochemical detection (LC-PED). The mobile phase consists of 1 volume of acetonitrile and 99 volumes of an aqueous solution containing 1.25% (v/v) trifluoroacetic acid, 0.025% (v/v) pentafluoropropionic acid and 0.85% (v/v) of 50% sodium hydroxide. The pH of the aqueous solution is adjusted to 2.6 with 0.5 M NaOH. The influence of the different chromatographic parameters on the separation was investigated. A quadruple-potential waveform was used as detection waveform. 0.5 M NaOH was added post column at a flow rate of 0.3 mL/min to raise the pH of detection to at least 12. The LOD and LOQ of micronomicin are 0.08 μg/mL (1.6 ng injected) and 0.25 μg/mL (5 ng injected), respectively. The linearity of micronomicin ranges from 0.25 to 60 μg/mL with a correlation coefficient of 0.