Synthesis Of Propionyl Levocarnitine Hydrochloride And Its Preparation

Propionyl Levocarnitine Hydrochloride ( PLC ) is the esterification derivative of Levocarnitine ( LC ), and has the similar physiological activity with LC. Its main pharmacological role is in improving the performance of the material and energy metabolism for damaged myocardium. At present only Italian Sigma-tau develop two preparations of PLC for the treatment of lower limb arterial pathological changes and chronic heart function failure. No domestic enterprise has been permitted to produce the drug. So PLC and two preparations were studied in this article and the structure characterization, the quality control in accordance with the criterion were also established.1. Synthesis of PLC. The PLC was synthesized from LC and propionyl chloride and identified by IR, MS, NMR as well as element analysis. The total yield was 51 %. This process has the advanatages of mild conditions, convenient operations as well as low cost.2. Quality control of PLC. HPLC was adopted for determination of PLC and the related substances in the bulk drug, the column was NH2 column ( Kromasil KR100-5, 250 mm×4.6 mm, 5μm ), the mobile phase was acetonitrile-0.05mol/L monopotassium phosphate ( 70:30 ), the detection wavelength was 205 nm. As well as GC and HPLC were used to determine the residue organic solvents of PLC. GC was used for determination of acetone. The column was PEG-20M capillary column ( 30 m×0.32 mm, 1μm); carrying gas was N2 and acetone was seperated completely through gradient temperature with flame ionization detector. RP-HPLC was adopted to determine propionic acid. The column was C18 (Hanban,150 mm×4.6 mm,5μm ), the mobile phase was 0.05 mol/L monopotassium phosphate, the detection wavelength was 210 nm. The methods have some advantages such as convenience, quickness and sensitiveness.3. Prepare PLC tablet and lyophilized powder and establish methods for their quality control. The prescriptions were filtered according to references and Pharmacopoeia, and the preparations complyed with the standards.