Boli vypracované modifikované postupy stanovenia obsahu vybratých solí dusík obsahujúcich organických zásad alkalimetrickou titráciou v prostredí etanolu 70 % a kyseliny chlorovodíkovej 0,01 mol/l, v prostredí samotného etanolu 70 %, resp. etanolu 96 % s potenciometrickou indikáciou konca titrácie. Výsledky stanovenia obsahu vybratých substancií liečiv porovnávame s výsledkami stanovenia obsahu týchto liečiv v Ph. Eur. 7 Ed. V skupine 11 nami analyzovaných liečiv predpisuje Ph. Eur. 7th Ed. uvedenú alkalimetrickú titráciu pre 8 liečiv: Cinchocaine hydrochloride, Codeine hydrochloride dihydrate, Ethylmorphine hydrochloride, Lidocaine hydrochloride, Papaverine hydrochloride, Pilocarpine hydrochloride, Quinine hydrochloride, Tetracaine hydrochloride. Pri 5 liečivách z tejto skupiny: Cinchocaine hydrochloride, Ethylmorphine hydrochloride, Papaverine hydrochloride, Pilocarpine hydrochloride a Tetracaine hydrochloride metóda neposkytuje výsledky zhodné s deklarovaným obsahom liečiv v príslušných liekopisných článkoch. Do súboru 11 analyzovaných liečiv sme zaradili aj liečivá charakteru slabých organických zásad, pre ktoré liekopis predpisuje iné postupy stanovenia obsahu: pre Thiamine hydrochloride a Pyridoxine hydrochloride je v liekopise predpísaná acidimetrická titrácia odmerným roztokom kyseliny chloristej v nevodnom prostredí a pre liečivo Procaine hydrochloride je to nitritometria, t.j. stanovenie dusíka v primárnych aromatických amínoch.

Modified methods – alkalimetry in ethanol 70% with a defined small volume of hydrochloric acid 0.01 mol/l added to the solution of the sample before the titration and alkalimetry in ethanol 70% or ethanol 96% alone with potentiometric end-point detection for the assay of halide salts of 11 organic N-bases has been investigated. The results were compared to those obtained by the method of the European Pharmacopoeia 7th Ed. (Ph. Eur. 7th Ed.). The Ph. Eur. 7th Ed. use for 8 investigated substances alkalimetry in alcohol 96 % with a defined small volume of hydrochloric acid 0.01 mol/l (5 ml) with potentiometric end-point detection: Cinchocaine hydrochloride, Codeine hydrochloride dihydrate, Ethylmorphine hydrochloride, Lidocaine hydrochloride, Papaverine hydrochloride, Pilocarpine hydrochloride, Quinine hydrochloride, Tetracaine hydrochloride. Our results revealed that the Ph. Eur. 7th Ed. method did not work for 5 drugs from this group: Cinchocaine hydrochloride, Ethylmorphine hydrochloride, Papaverine hydrochloride, Pilocarpine hydrochloride and Tetracaine hydrochloride. In the group of investigated substances we included also drugs with the character of weak organic bases for which Ph. Eur. 7th Ed. prescribed different methods for their assay: Thiamine hydrochloride and Pyridoxine hydrochloride – acidimetric titration in non-aqueous solvents with perchloric acid and Procaine hydrochloride – determination of primary aromatic amino-nitrogen (Ph. Eur. 7th Ed., chapter 2.5.8).

Katedra farmaceutickej chémie FaF Univ Komenského Bratislava

Alkalimetric titrations of salts of organic bases in the Pharmacopoeia