CS263884B1 - A method for determining desacetylmetipranolol in a biological material - Google Patents

Abstract

The method for determining desacetylmetipranolol in biological material consists of extracting the biological material with an organic solvent, e.g. a chlorinated hydrocarbon, which is evaporated and the residue is analyzed by high-performance liquid chromatography with electrochemical detection. Pindolol is used as an internal standard. The proposed method of determination is applicable for monitoring the treatment of patients with metipranolol (Trime- (pranol SPOFA) and for pharmacokinetic (metipranolol studies.

Description

Desacetylmetipranolol (DM) is a pharmacologically active metaholite of the original Czechoslovak non-selective beta-symipatolytic metipranol, produced under the name Trimepranol SPOFA (i.e. ID mg or 40 mg) and used as a sympathosilytic, antiarrhythmic and antihypertensive agent. DM results from desacetylation of trimepranol immediately after administration to the body. In terms of monitored treatment of patients, it is therefore necessary to monitor and determine the level of DM. DM has been described in the literature by gas chromatography in conjunction with mass spectrometry (GC-MS) and by thin-layer chromatography (TLC) with thensitometric evaluation.

The disadvantage of the GC-MS method is the high acquisition cost of the mass spectrometer, the TLC method does not have sufficient sensitivity to monitor plasma DM levels. High performance liquid chromatography has not been used hitherto.

The determination of tiesacetylmethylpranolol in a biological material according to the invention consists in extracting the active substance in an organic solvent, e.g. a chlorinated hydrocarbon, followed by evaporation of the organic phase and liquid analysis by chromatography. dissolved residue.

Preferably, in clinical monitoring of DM levels, blood plasma is used as a sample, dichloromethane as an extraction solvent, and high performance liquid chromatography with electrochemical detection as an analytical method.

The method of determination of desacetylmetipranolol in biological material after extraction with organic solvent and evaporation of the solvent used, characterized in that the annual sample treatment uses readily available pindolol as an internal standard and allows the calibration method to be used curves. The iReóover.y method is 83%.

The relative standard deviation for 25 ng / ml plasma is 6.4%, for 50 ng / ml plasma is 4.8%. The detection limit of the method is 2 ng / 1 ml of plasma.

Exemplary embodiment

To 1.0 ml of plasma add 25.0 mg of pindolol, 300 μΐ 0.2 mol / l NaOH and shake with 2X5 ml of dichloromethane of suitable purity. The combined fractions were evaporated to dryness in a vacuum evaporator. Dissolve the residue in 0.50 ml of mobile phase and inject immediately .20 μΐ onto a liquid chromatograph column. As a mobile phase, a solution of: 600 ml 0.05 mol / 1 H 3 PO 4 400 ml methanol-ry 5 mg NaEDTA; The pH phase was. NaOH to 3.0. Suitable chromatographic column material is 5 μπι ODS (C 18), 50 ° C column temperature and 0.8 ml flow rate per minute. An electrochemical detector is suitable for detection. -. .....

Results

Applying the method to real samples 90 min after administration of Trimepranol SPOFA tablets to two healthy volunteers found 38 ng and 100 ng, respectively. 43 ng of desacetylmetipranolol in 1 ml of their plasma.

Claims (1)

The desacetylmetipranolol is determined in the evaporator by high performance liquid chromatography, preferably with electrochemical detection, using an internal standard.