Liquid chromatography and liquid chromatography-mass spectrometry analysis of donepezil degradation products
Analiza degradacionih proizvoda donepezila primenom tečne hromatografije i tečne hromatografije-masene spektrometrije
2015
Аутори
Mladenović, Aleksandar R.Jadranin, Milka
Pavlović, Aleksandar D.
Petrović, Slobodan
Drmanić, Saša
Avramov-Ivić, Milka
Mijin, Dušan
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
Кључне речи:
donepezil hydrochloride / forced degradation / stability-indicating HPLC method / liquid chromatography-mass spectrometry / donepezil-hidrohlorid / forsirana degradacija / HPLC metoda za određivanje stabilnosti / tečna hromatografija-masena spektrometrijaИзвор:
Chemical Industry & Chemical Engineering Quarterly, 2015, 21, 3, 447-455Издавач:
- Association of the Chemical Engineers of Serbia
Финансирање / пројекти:
- Проучавање синтезе, структуре и активности органских једињења природног и синтетског порекла (RS-MESTD-Basic Research (BR or ON)-172013)
DOI: 10.2298/CICEQ141023047M
ISSN: 1451-9372
WoS: 000360690200009
Scopus: 2-s2.0-84940536168
Институција/група
Tehnološko-metalurški fakultetTY - JOUR AU - Mladenović, Aleksandar R. AU - Jadranin, Milka AU - Pavlović, Aleksandar D. AU - Petrović, Slobodan AU - Drmanić, Saša AU - Avramov-Ivić, Milka AU - Mijin, Dušan PY - 2015 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/2927 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 & Chemical Engineering Quarterly 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 EP - 455 IS - 3 SP - 447 VL - 21 DO - 10.2298/CICEQ141023047M ER -
@article{ author = "Mladenović, Aleksandar R. and Jadranin, Milka and Pavlović, Aleksandar D. and Petrović, Slobodan and Drmanić, Saša and Avramov-Ivić, Milka and Mijin, Dušan", year = "2015", 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 & Chemical Engineering Quarterly", 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", pages = "455-447", number = "3", volume = "21", doi = "10.2298/CICEQ141023047M" }
Mladenović, A. R., Jadranin, M., Pavlović, A. D., Petrović, S., Drmanić, S., Avramov-Ivić, M.,& Mijin, D.. (2015). Liquid chromatography and liquid chromatography-mass spectrometry analysis of donepezil degradation products. in Chemical Industry & Chemical Engineering Quarterly Association of the Chemical Engineers of Serbia., 21(3), 447-455. https://doi.org/10.2298/CICEQ141023047M
Mladenović AR, Jadranin M, Pavlović AD, Petrović S, Drmanić S, Avramov-Ivić M, Mijin D. Liquid chromatography and liquid chromatography-mass spectrometry analysis of donepezil degradation products. in Chemical Industry & Chemical Engineering Quarterly. 2015;21(3):447-455. doi:10.2298/CICEQ141023047M .
Mladenović, Aleksandar R., Jadranin, Milka, Pavlović, Aleksandar D., Petrović, Slobodan, Drmanić, Saša, Avramov-Ivić, Milka, Mijin, Dušan, "Liquid chromatography and liquid chromatography-mass spectrometry analysis of donepezil degradation products" in Chemical Industry & Chemical Engineering Quarterly, 21, no. 3 (2015):447-455, https://doi.org/10.2298/CICEQ141023047M . .