Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer
Novi pristup u razvoju (U)HPLC gradijentnih metoda koji bi omogućio uspešan transfer
Аутори
Protić, AnaMilenković, Milan
Rašević, Marija
Otašević, Biljana
Zečević, Mira
Krmar, Jovana
Malenović, Anđelija
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Nowadays, one of the ultimate requirements in drug analysis is rapid method
development, prompt chromatographic run time and long lasting method’s lifecycle. Special
attention should be paid to development of gradient elution (U)HPLC methods that are
commonly related to troubleshooting during the inter-laboratory method transfer. The dwell
volume difference between (U)HPLC systems is the main reason for this issue (1). The aim of
this study was to propose new gradient method development methodology with integrated
dwell volumes values in the optimization process. This is especially useful approach for
industry where is frequently known which (U)HPLC instruments will be applied for drug
analysis. Proposed methodology was tested on the model mixture which encompassed
dabigatran etexilate mesylate and its nine impurities. Experimental design methodology and
three different (U)HPLC instruments with significant dwell volume differences were utilized.
Statistically significant var...iables were selected with Plackett-Burman design, and along with
dwell volume values were included in D-optimal design. The separation criteria s between
adjacent peaks was selected as output for method optimization. Indirect modelling together
with Monte Carlo simulations enabled selection of optimal and robust chromatographic
conditions joint for all instruments. The optimal conditions included 24% (v/v) of initial
amount of acetonitrile, 54% (v/v) of the final amount of acetonitrile, 15 min of gradient
elution run time and pH value equal to 4.9. The proposed method utility was proved since it
was successfully validated and met all validation criteria (2).
U današnje vreme, jedan od važnih zahteva prilikom razvoja hromatografskih metoda
jeste da se razvoj uradi brzo, da vreme trajanja hromatografske analize bude kratko i da se
obezbedi dug životni ciklus metode. Posebnu pažnju treba obratiti na (U)HPLC metode sa
gradijentnim eluiranjem kod kojih se često javljaju problemi prilikom međulaboratorijskog
transfera. Glavni razlog za zahtevan transfer gradijentnih (U)HPLC metoda je razlika u
vrednostima dwell volume između (U)HPLC uređaja (1). Cilj ovog rada je bio da predloži
novu metodologiju razvoja gradijentnih (U)HPLC metoda, pri čemu će vrednosti dwell
volumes biti integrisane sa drugim ulaznim promenljivama u fazi optimizacije. Ovo bi bio
posebno koristan pristup u industriji gde se obično zna na kojim će sve (U)HPLC
instrumentima metoda biti korišćena. Metodologija je testirana na smeši dabigatran eteksilat
mezilata i njegovih devet nečistoća. Za razvoj metode korišćen je eksperimentalni dizajn i tri
različita (U)HPLC instru...menta sa značajnim razlikama u dwell volume vrednostima.
Statistički značajne ulazne promenljive su dobijene primenom Plackett‐Burman dizajna, i
zajedno sa vrednostima dwell volume su bile uključene u D‐opimal dizajn. Kriterijum
razdvajanja s između susednih parova pikova odabran je kao odgovor u odnosu na koji je
metoda optimizovana. Indirektno modelovanje zajedno sa Monte Karlo simulacijom
omoguć ilo je izbor optimalnih i robusnih hromatografskih uslova zajedničkih za sva tri
instrumenta. Oni su uključivali 24% (v/v) početnog udela acetonitrila, 54% (v/v) finalnog
udela acetonitrila, vreme trajanja gradijenta od 15 minuta i pH vrednost 4,9. Primenljivost
predložene metodologije je dokazana, jer je dobijena metoda uspešno validirana na sva tri
(U)HPLC instrumenta (2).
Извор:
Arhiv za farmaciju, 2022, 72, 4 suplement, S55-S56Издавач:
- Savez farmaceutskih udruženja Srbije (SFUS)
Финансирање / пројекти:
Напомена:
- VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd
Институција/група
PharmacyTY - CONF AU - Protić, Ana AU - Milenković, Milan AU - Rašević, Marija AU - Otašević, Biljana AU - Zečević, Mira AU - Krmar, Jovana AU - Malenović, Anđelija PY - 2022 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4446 AB - Nowadays, one of the ultimate requirements in drug analysis is rapid method development, prompt chromatographic run time and long lasting method’s lifecycle. Special attention should be paid to development of gradient elution (U)HPLC methods that are commonly related to troubleshooting during the inter-laboratory method transfer. The dwell volume difference between (U)HPLC systems is the main reason for this issue (1). The aim of this study was to propose new gradient method development methodology with integrated dwell volumes values in the optimization process. This is especially useful approach for industry where is frequently known which (U)HPLC instruments will be applied for drug analysis. Proposed methodology was tested on the model mixture which encompassed dabigatran etexilate mesylate and its nine impurities. Experimental design methodology and three different (U)HPLC instruments with significant dwell volume differences were utilized. Statistically significant variables were selected with Plackett-Burman design, and along with dwell volume values were included in D-optimal design. The separation criteria s between adjacent peaks was selected as output for method optimization. Indirect modelling together with Monte Carlo simulations enabled selection of optimal and robust chromatographic conditions joint for all instruments. The optimal conditions included 24% (v/v) of initial amount of acetonitrile, 54% (v/v) of the final amount of acetonitrile, 15 min of gradient elution run time and pH value equal to 4.9. The proposed method utility was proved since it was successfully validated and met all validation criteria (2). AB - U današnje vreme, jedan od važnih zahteva prilikom razvoja hromatografskih metoda jeste da se razvoj uradi brzo, da vreme trajanja hromatografske analize bude kratko i da se obezbedi dug životni ciklus metode. Posebnu pažnju treba obratiti na (U)HPLC metode sa gradijentnim eluiranjem kod kojih se često javljaju problemi prilikom međulaboratorijskog transfera. Glavni razlog za zahtevan transfer gradijentnih (U)HPLC metoda je razlika u vrednostima dwell volume između (U)HPLC uređaja (1). Cilj ovog rada je bio da predloži novu metodologiju razvoja gradijentnih (U)HPLC metoda, pri čemu će vrednosti dwell volumes biti integrisane sa drugim ulaznim promenljivama u fazi optimizacije. Ovo bi bio posebno koristan pristup u industriji gde se obično zna na kojim će sve (U)HPLC instrumentima metoda biti korišćena. Metodologija je testirana na smeši dabigatran eteksilat mezilata i njegovih devet nečistoća. Za razvoj metode korišćen je eksperimentalni dizajn i tri različita (U)HPLC instrumenta sa značajnim razlikama u dwell volume vrednostima. Statistički značajne ulazne promenljive su dobijene primenom Plackett‐Burman dizajna, i zajedno sa vrednostima dwell volume su bile uključene u D‐opimal dizajn. Kriterijum razdvajanja s između susednih parova pikova odabran je kao odgovor u odnosu na koji je metoda optimizovana. Indirektno modelovanje zajedno sa Monte Karlo simulacijom omoguć ilo je izbor optimalnih i robusnih hromatografskih uslova zajedničkih za sva tri instrumenta. Oni su uključivali 24% (v/v) početnog udela acetonitrila, 54% (v/v) finalnog udela acetonitrila, vreme trajanja gradijenta od 15 minuta i pH vrednost 4,9. Primenljivost predložene metodologije je dokazana, jer je dobijena metoda uspešno validirana na sva tri (U)HPLC instrumenta (2). PB - Savez farmaceutskih udruženja Srbije (SFUS) C3 - Arhiv za farmaciju T1 - Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer T1 - Novi pristup u razvoju (U)HPLC gradijentnih metoda koji bi omogućio uspešan transfer VL - 72 IS - 4 suplement SP - S55 EP - S56 UR - https://hdl.handle.net/21.15107/rcub_farfar_4446 ER -
@conference{ author = "Protić, Ana and Milenković, Milan and Rašević, Marija and Otašević, Biljana and Zečević, Mira and Krmar, Jovana and Malenović, Anđelija", year = "2022", abstract = "Nowadays, one of the ultimate requirements in drug analysis is rapid method development, prompt chromatographic run time and long lasting method’s lifecycle. Special attention should be paid to development of gradient elution (U)HPLC methods that are commonly related to troubleshooting during the inter-laboratory method transfer. The dwell volume difference between (U)HPLC systems is the main reason for this issue (1). The aim of this study was to propose new gradient method development methodology with integrated dwell volumes values in the optimization process. This is especially useful approach for industry where is frequently known which (U)HPLC instruments will be applied for drug analysis. Proposed methodology was tested on the model mixture which encompassed dabigatran etexilate mesylate and its nine impurities. Experimental design methodology and three different (U)HPLC instruments with significant dwell volume differences were utilized. Statistically significant variables were selected with Plackett-Burman design, and along with dwell volume values were included in D-optimal design. The separation criteria s between adjacent peaks was selected as output for method optimization. Indirect modelling together with Monte Carlo simulations enabled selection of optimal and robust chromatographic conditions joint for all instruments. The optimal conditions included 24% (v/v) of initial amount of acetonitrile, 54% (v/v) of the final amount of acetonitrile, 15 min of gradient elution run time and pH value equal to 4.9. The proposed method utility was proved since it was successfully validated and met all validation criteria (2)., U današnje vreme, jedan od važnih zahteva prilikom razvoja hromatografskih metoda jeste da se razvoj uradi brzo, da vreme trajanja hromatografske analize bude kratko i da se obezbedi dug životni ciklus metode. Posebnu pažnju treba obratiti na (U)HPLC metode sa gradijentnim eluiranjem kod kojih se često javljaju problemi prilikom međulaboratorijskog transfera. Glavni razlog za zahtevan transfer gradijentnih (U)HPLC metoda je razlika u vrednostima dwell volume između (U)HPLC uređaja (1). Cilj ovog rada je bio da predloži novu metodologiju razvoja gradijentnih (U)HPLC metoda, pri čemu će vrednosti dwell volumes biti integrisane sa drugim ulaznim promenljivama u fazi optimizacije. Ovo bi bio posebno koristan pristup u industriji gde se obično zna na kojim će sve (U)HPLC instrumentima metoda biti korišćena. Metodologija je testirana na smeši dabigatran eteksilat mezilata i njegovih devet nečistoća. Za razvoj metode korišćen je eksperimentalni dizajn i tri različita (U)HPLC instrumenta sa značajnim razlikama u dwell volume vrednostima. Statistički značajne ulazne promenljive su dobijene primenom Plackett‐Burman dizajna, i zajedno sa vrednostima dwell volume su bile uključene u D‐opimal dizajn. Kriterijum razdvajanja s između susednih parova pikova odabran je kao odgovor u odnosu na koji je metoda optimizovana. Indirektno modelovanje zajedno sa Monte Karlo simulacijom omoguć ilo je izbor optimalnih i robusnih hromatografskih uslova zajedničkih za sva tri instrumenta. Oni su uključivali 24% (v/v) početnog udela acetonitrila, 54% (v/v) finalnog udela acetonitrila, vreme trajanja gradijenta od 15 minuta i pH vrednost 4,9. Primenljivost predložene metodologije je dokazana, jer je dobijena metoda uspešno validirana na sva tri (U)HPLC instrumenta (2).", publisher = "Savez farmaceutskih udruženja Srbije (SFUS)", journal = "Arhiv za farmaciju", title = "Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer, Novi pristup u razvoju (U)HPLC gradijentnih metoda koji bi omogućio uspešan transfer", volume = "72", number = "4 suplement", pages = "S55-S56", url = "https://hdl.handle.net/21.15107/rcub_farfar_4446" }
Protić, A., Milenković, M., Rašević, M., Otašević, B., Zečević, M., Krmar, J.,& Malenović, A.. (2022). Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer. in Arhiv za farmaciju Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S55-S56. https://hdl.handle.net/21.15107/rcub_farfar_4446
Protić A, Milenković M, Rašević M, Otašević B, Zečević M, Krmar J, Malenović A. Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer. in Arhiv za farmaciju. 2022;72(4 suplement):S55-S56. https://hdl.handle.net/21.15107/rcub_farfar_4446 .
Protić, Ana, Milenković, Milan, Rašević, Marija, Otašević, Biljana, Zečević, Mira, Krmar, Jovana, Malenović, Anđelija, "Novel Gradient Elution (U)HPLC Method Development that Enables Successful Method Transfer" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S55-S56, https://hdl.handle.net/21.15107/rcub_farfar_4446 .