A. P. Arzamastsev, T. Y. Luttseva, N. P. Sadchikova
Nov 1, 1999
Citations
0
Influential Citations
1
Citations
Journal
Pharmaceutical Chemistry Journal
Abstract
Suxamethonium iodide is a succinic acid derivative that is widely used in medicine. In particular, the injection forms of this drug (e.g., bis-[2-(trimethylammonium)ethyl]succinate diiodide) are used as depolarizing muscular relaxants in surgery. In Russia, suxamethonium iodide (registered under the trade name of ditilin) was synthesized for the first time in 1998 using an original technological scheme developed at the Research Institute of Organic Semiproducts and Dyes (State Scientific Center, Moscow). The commercial production of this drug became possible when the Ministry of Public Health validated the corresponding temporal pharmacopoeial clause (VFS 42-2810-96 replacing FS 42-2810-91) [1]. In preparing the new pharmacopoeial clause, special attention was paid to the method of determining host impurities (choline iodide, succinylmonocholine iodide, and unreacted residue of succinic acid esters), the presence of which may be caused by violation of the drug production technology. According to foreign pharmacopoeias, the impurities in suxamethonium iodide [2], suxamethonium bromide [3, 4], and suxamethonium chloride [5 12] are determined by TLC under various conditions (Table 1). According to the old pharmacopoeial clause (FS 42-2819 91), the impurities had to be determined by applying an aqueous drug solution (containing 175 pg of the parent substance) onto a high-performance TLC Armsorb VETSKh Si 10 plate. Verification of this procedure on commercial batches of ditilin obtained at the Research Institute of Organic Semiproducts and Dyes showed that the samples form strongly elongated (up to 4 era) bands originating from the start line, which was explained by overloading of the sorbent plate. This Circumstance, as well the necessity of keeping the plate for a long time before and after treatment with Dragendorff reagent (more than two hours) and a low