This study describes the investigation of degradation products of donepezil (DP) using a stability-indicating RP-HPLC method for determination of donepezil, which is a centrally acting reversible acetyl cholinesterase inhibitor. In order to investigate the stability of the drug and formed degradation products, a forced degradation study of the drug sample and finished product under different forced degradation conditions was conducted. Donepezil hydrochloride and donepezil tablets were subjected to stress degradation conditions recommended by the International Conference on Harmonization (ICH). Donepezil hydrochloride solutions were subjected to acid and alkali hydrolysis, chemical oxidation and thermal degradation. Significant degradation was observed under alkali hydrolysis and oxidative degradation conditions. Additional degradation products were observed under the conditions of oxidative degradation. The degradation products observed during forced degradation studies were monitored... using the developed high performance liquid chromatography (HPLC) method. The parent method was modified in order to obtain LC-MS compatible method, which was used to identify the degradation products from forced degradation samples using high resolution mass spectrometry. The mass spectrum provided the precise mass from which the molecular formula of the drug substance and formed degradation products was derived, and proved the specificity of the method unambiguously.
Proučavanje degradacionih proizvoda donepezila je izvršeno korišćenjem RP-HPLC metode za određivanje stabilnosti donepezila, leka koji pripada grupi reverzibilnih inhibitora acetilholinesteraze. U cilju ispitivanja stabilnosti leka i njegovih degradacionih proizvoda sprovedena je studija forsirane degradacije čiste supstance kao i farmaceutskog proizvoda pod različitim uslovima. Donepezil-hidrohlorid i donepezil tablete su podvrgnuti različitim uslovima degradacije prema preporukama Internacionalne konferencije za harmonizaciju. Rastvori donepezil-hidrohlorida su podvrgnuti kiseloj i baznoj hidrolizi, hemijskoj oksidaciji i termalnoj degradaciji. Pri baznoj hidrolizi i hemijskoj oksidaciji uočena je značajna degradacija polaznog molekula. Oksidativnom degradacijom nastaju i proizvodi koji nisu uočeni kod ostalih postupaka forsirane degradacije. Nastali proizvodi analizirani su novorazvijenom HPLC metodom. Osnovna metoda je modifikovana u cilju dobijanja LC-MS kompatibilne metode kako b...i se identifikovali nastali degradacioni proizvodi. Na osnovu resultata dobijenih masenom spektrometrijom dobijene su tačne mase proizvoda degradacije, čime je omogućeno određivanje njihovih molekulskih formula.
TY - JOUR
AU - Mladenović, Aleksandar R.
AU - Jadranin, Milka
AU - Pavlović, Aleksandar D.
AU - Petrović, Slobodan D.
AU - Drmanić, Saša Ž.
AU - Avramov Ivić, Milka
AU - Mijin, Dušan
PY - 2015
UR - http://cer.ihtm.bg.ac.rs/handle/123456789/1731
AB - This study describes the investigation of degradation products of donepezil (DP) using a stability-indicating RP-HPLC method for determination of donepezil, which is a centrally acting reversible acetyl cholinesterase inhibitor. In order to investigate the stability of the drug and formed degradation products, a forced degradation study of the drug sample and finished product under different forced degradation conditions was conducted. Donepezil hydrochloride and donepezil tablets were subjected to stress degradation conditions recommended by the International Conference on Harmonization (ICH). Donepezil hydrochloride solutions were subjected to acid and alkali hydrolysis, chemical oxidation and thermal degradation. Significant degradation was observed under alkali hydrolysis and oxidative degradation conditions. Additional degradation products were observed under the conditions of oxidative degradation. The degradation products observed during forced degradation studies were monitored using the developed high performance liquid chromatography (HPLC) method. The parent method was modified in order to obtain LC-MS compatible method, which was used to identify the degradation products from forced degradation samples using high resolution mass spectrometry. The mass spectrum provided the precise mass from which the molecular formula of the drug substance and formed degradation products was derived, and proved the specificity of the method unambiguously.
AB - Proučavanje degradacionih proizvoda donepezila je izvršeno korišćenjem RP-HPLC metode za određivanje stabilnosti donepezila, leka koji pripada grupi reverzibilnih inhibitora acetilholinesteraze. U cilju ispitivanja stabilnosti leka i njegovih degradacionih proizvoda sprovedena je studija forsirane degradacije čiste supstance kao i farmaceutskog proizvoda pod različitim uslovima. Donepezil-hidrohlorid i donepezil tablete su podvrgnuti različitim uslovima degradacije prema preporukama Internacionalne konferencije za harmonizaciju. Rastvori donepezil-hidrohlorida su podvrgnuti kiseloj i baznoj hidrolizi, hemijskoj oksidaciji i termalnoj degradaciji. Pri baznoj hidrolizi i hemijskoj oksidaciji uočena je značajna degradacija polaznog molekula. Oksidativnom degradacijom nastaju i proizvodi koji nisu uočeni kod ostalih postupaka forsirane degradacije. Nastali proizvodi analizirani su novorazvijenom HPLC metodom. Osnovna metoda je modifikovana u cilju dobijanja LC-MS kompatibilne metode kako bi se identifikovali nastali degradacioni proizvodi. Na osnovu resultata dobijenih masenom spektrometrijom dobijene su tačne mase proizvoda degradacije, čime je omogućeno određivanje njihovih molekulskih formula.
PB - Association of the Chemical Engineers of Serbia
T2 - Chemical Industry and Chemical Engineering Quarterly / CICEQ
T1 - Liquid chromatography and liquid chromatography-mass spectrometry analysis of donepezil degradation products
T1 - Analiza degradacionih proizvoda donepezila primenom tečne hromatografije i tečne hromatografije-masene spektrometrije
VL - 21
IS - 3
SP - 447
EP - 455
DO - 10.2298/CICEQ141023047M
ER -
@article{
author = "Mladenović, Aleksandar R. and Jadranin, Milka and Pavlović, Aleksandar D. and Petrović, Slobodan D. and Drmanić, Saša Ž. and Avramov Ivić, Milka and Mijin, Dušan",
year = "2015",
url = "http://cer.ihtm.bg.ac.rs/handle/123456789/1731",
abstract = "This study describes the investigation of degradation products of donepezil (DP) using a stability-indicating RP-HPLC method for determination of donepezil, which is a centrally acting reversible acetyl cholinesterase inhibitor. In order to investigate the stability of the drug and formed degradation products, a forced degradation study of the drug sample and finished product under different forced degradation conditions was conducted. Donepezil hydrochloride and donepezil tablets were subjected to stress degradation conditions recommended by the International Conference on Harmonization (ICH). Donepezil hydrochloride solutions were subjected to acid and alkali hydrolysis, chemical oxidation and thermal degradation. Significant degradation was observed under alkali hydrolysis and oxidative degradation conditions. Additional degradation products were observed under the conditions of oxidative degradation. The degradation products observed during forced degradation studies were monitored using the developed high performance liquid chromatography (HPLC) method. The parent method was modified in order to obtain LC-MS compatible method, which was used to identify the degradation products from forced degradation samples using high resolution mass spectrometry. The mass spectrum provided the precise mass from which the molecular formula of the drug substance and formed degradation products was derived, and proved the specificity of the method unambiguously., Proučavanje degradacionih proizvoda donepezila je izvršeno korišćenjem RP-HPLC metode za određivanje stabilnosti donepezila, leka koji pripada grupi reverzibilnih inhibitora acetilholinesteraze. U cilju ispitivanja stabilnosti leka i njegovih degradacionih proizvoda sprovedena je studija forsirane degradacije čiste supstance kao i farmaceutskog proizvoda pod različitim uslovima. Donepezil-hidrohlorid i donepezil tablete su podvrgnuti različitim uslovima degradacije prema preporukama Internacionalne konferencije za harmonizaciju. Rastvori donepezil-hidrohlorida su podvrgnuti kiseloj i baznoj hidrolizi, hemijskoj oksidaciji i termalnoj degradaciji. Pri baznoj hidrolizi i hemijskoj oksidaciji uočena je značajna degradacija polaznog molekula. Oksidativnom degradacijom nastaju i proizvodi koji nisu uočeni kod ostalih postupaka forsirane degradacije. Nastali proizvodi analizirani su novorazvijenom HPLC metodom. Osnovna metoda je modifikovana u cilju dobijanja LC-MS kompatibilne metode kako bi se identifikovali nastali degradacioni proizvodi. Na osnovu resultata dobijenih masenom spektrometrijom dobijene su tačne mase proizvoda degradacije, čime je omogućeno određivanje njihovih molekulskih formula.",
publisher = "Association of the Chemical Engineers of Serbia",
journal = "Chemical Industry and Chemical Engineering Quarterly / CICEQ",
title = "Liquid chromatography and liquid chromatography-mass spectrometry analysis of donepezil degradation products, Analiza degradacionih proizvoda donepezila primenom tečne hromatografije i tečne hromatografije-masene spektrometrije",
volume = "21",
number = "3",
pages = "447-455",
doi = "10.2298/CICEQ141023047M"
}
Mladenović AR, Jadranin M, Pavlović AD, Petrović SD, Drmanić SŽ, Avramov Ivić M, Mijin D. Analiza degradacionih proizvoda donepezila primenom tečne hromatografije i tečne hromatografije-masene spektrometrije. Chemical Industry and Chemical Engineering Quarterly / CICEQ. 2015;21(3):447-455
Mladenović, A. R., Jadranin, M., Pavlović, A. D., Petrović, S. D., Drmanić, S. Ž., Avramov Ivić, M.,& Mijin, D. (2015). Analiza degradacionih proizvoda donepezila primenom tečne hromatografije i tečne hromatografije-masene spektrometrije.
Chemical Industry and Chemical Engineering Quarterly / CICEQAssociation of the Chemical Engineers of Serbia., 21(3), 447-455.
https://doi.org/10.2298/CICEQ141023047M
Mladenović Aleksandar R., Jadranin Milka, Pavlović Aleksandar D., Petrović Slobodan D., Drmanić Saša Ž., Avramov Ivić Milka, Mijin Dušan, "Analiza degradacionih proizvoda donepezila primenom tečne hromatografije i tečne hromatografije-masene spektrometrije" 21, no. 3 (2015):447-455,
https://doi.org/10.2298/CICEQ141023047M .
