Methylprednisolone and its related substances in freeze-dried powders for injections
Metilprednizolon i njegove srodne supstance u liofilizatu za rastvor za injekcije
Апстракт
In this work, the behavior of the active pharmaceutical substances methylprednisolone (in a form of methylprednisolone sodium succinate) in finished pharmaceutical dosage form, i.e., freeze-dried powder for injections, was examined. The goal was to evaluate the chemical stabilities of methylprednisolone sodium succinate packaged in a dual chamber vial, as a specific container closure system. The effect of different parameters: temperature, moisture and light were monitored. The method proposed by United States Pharmacopeia was used to determine concentrations of methylprednisolone, as the sum of the concentration of methylprednisolone esters (17-hydrogen succinate and 21-hydrogen succinate) and free methylprednisolone. The HPLC method was used for stability evaluation of the active substance and determination of related substances. Four main degradation products were registered. Temperature has a major impact on the degradation process with the appearance of 3 degradation products (imp...urities B, C and D), while the presence of light caused an increasing content of impurity A. Identification of impurity B, C and D has been realized using mass and NMR spectroscopy. All three substances are substances related to methylprednisolone.
U ovom radu ispitivane su osobine farmakološki aktivne supstance metilprednizolona (u obliku metilprednizolon-natrijum-sukcinata) u gotovom proizvodu - liofilizatu za rastvor za injekcije. Cilj rada je ispitivanje hemijske stabilnosti metilpredni-zolon-natrijum-sukcinata u dvokomornoj bočici, kao specifičnom sistemu kontaktnog pakovanja. Ispitan je efekat različitih parametara: temperature, vlage i svetlosti. Za određivanje koncentracije metilprednizolona, kao zbirne koncentracije metilprednizolon estara (17-hidrogen-sukcinata i 21-hidrogen-sukcinata) i slobodnog metilprednizolona, korišćena je metoda opisana u Američkoj farmakopeji. Za ispitivanje srodnih supstanci primenjena je HPLC metoda. Uočena su 4 degradaciona proizvoda. Dokazano je da povećanje temperature ima najveći značaj na proces degradacije i utiče na povećanje sadržaja nečistoća B, C i D, dok prisustvo svetlosti dovodi do povećanja sadržaja nečistoće A. Nečistoće B, C i D su identifikovane primenom masene i NMR spektrosk...opije. Sve tri nečistoće su identifikovane kao srodne supstance metilprednizolona.
Кључне речи:
methylprednisolone sodium succinate / freeze-dried powder / container closure system / stability / impuritiesИзвор:
Journal of the Serbian Chemical Society, 2010, 75, 10, 1441-1452Издавач:
- Srpsko hemijsko društvo, Beograd
Финансирање / пројекти:
DOI: 10.2298/JSC100115087S
ISSN: 0352-5139
WoS: 000283895200013
Scopus: 2-s2.0-78449271200
Институција/група
PharmacyTY - JOUR AU - Solomun, Ljiljana AU - Ibrić, Svetlana AU - Vajs, Vlatka AU - Vucković, Ivan M. AU - Vujić, Zorica PY - 2010 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1426 AB - In this work, the behavior of the active pharmaceutical substances methylprednisolone (in a form of methylprednisolone sodium succinate) in finished pharmaceutical dosage form, i.e., freeze-dried powder for injections, was examined. The goal was to evaluate the chemical stabilities of methylprednisolone sodium succinate packaged in a dual chamber vial, as a specific container closure system. The effect of different parameters: temperature, moisture and light were monitored. The method proposed by United States Pharmacopeia was used to determine concentrations of methylprednisolone, as the sum of the concentration of methylprednisolone esters (17-hydrogen succinate and 21-hydrogen succinate) and free methylprednisolone. The HPLC method was used for stability evaluation of the active substance and determination of related substances. Four main degradation products were registered. Temperature has a major impact on the degradation process with the appearance of 3 degradation products (impurities B, C and D), while the presence of light caused an increasing content of impurity A. Identification of impurity B, C and D has been realized using mass and NMR spectroscopy. All three substances are substances related to methylprednisolone. AB - U ovom radu ispitivane su osobine farmakološki aktivne supstance metilprednizolona (u obliku metilprednizolon-natrijum-sukcinata) u gotovom proizvodu - liofilizatu za rastvor za injekcije. Cilj rada je ispitivanje hemijske stabilnosti metilpredni-zolon-natrijum-sukcinata u dvokomornoj bočici, kao specifičnom sistemu kontaktnog pakovanja. Ispitan je efekat različitih parametara: temperature, vlage i svetlosti. Za određivanje koncentracije metilprednizolona, kao zbirne koncentracije metilprednizolon estara (17-hidrogen-sukcinata i 21-hidrogen-sukcinata) i slobodnog metilprednizolona, korišćena je metoda opisana u Američkoj farmakopeji. Za ispitivanje srodnih supstanci primenjena je HPLC metoda. Uočena su 4 degradaciona proizvoda. Dokazano je da povećanje temperature ima najveći značaj na proces degradacije i utiče na povećanje sadržaja nečistoća B, C i D, dok prisustvo svetlosti dovodi do povećanja sadržaja nečistoće A. Nečistoće B, C i D su identifikovane primenom masene i NMR spektroskopije. Sve tri nečistoće su identifikovane kao srodne supstance metilprednizolona. PB - Srpsko hemijsko društvo, Beograd T2 - Journal of the Serbian Chemical Society T1 - Methylprednisolone and its related substances in freeze-dried powders for injections T1 - Metilprednizolon i njegove srodne supstance u liofilizatu za rastvor za injekcije VL - 75 IS - 10 SP - 1441 EP - 1452 DO - 10.2298/JSC100115087S ER -
@article{ author = "Solomun, Ljiljana and Ibrić, Svetlana and Vajs, Vlatka and Vucković, Ivan M. and Vujić, Zorica", year = "2010", abstract = "In this work, the behavior of the active pharmaceutical substances methylprednisolone (in a form of methylprednisolone sodium succinate) in finished pharmaceutical dosage form, i.e., freeze-dried powder for injections, was examined. The goal was to evaluate the chemical stabilities of methylprednisolone sodium succinate packaged in a dual chamber vial, as a specific container closure system. The effect of different parameters: temperature, moisture and light were monitored. The method proposed by United States Pharmacopeia was used to determine concentrations of methylprednisolone, as the sum of the concentration of methylprednisolone esters (17-hydrogen succinate and 21-hydrogen succinate) and free methylprednisolone. The HPLC method was used for stability evaluation of the active substance and determination of related substances. Four main degradation products were registered. Temperature has a major impact on the degradation process with the appearance of 3 degradation products (impurities B, C and D), while the presence of light caused an increasing content of impurity A. Identification of impurity B, C and D has been realized using mass and NMR spectroscopy. All three substances are substances related to methylprednisolone., U ovom radu ispitivane su osobine farmakološki aktivne supstance metilprednizolona (u obliku metilprednizolon-natrijum-sukcinata) u gotovom proizvodu - liofilizatu za rastvor za injekcije. Cilj rada je ispitivanje hemijske stabilnosti metilpredni-zolon-natrijum-sukcinata u dvokomornoj bočici, kao specifičnom sistemu kontaktnog pakovanja. Ispitan je efekat različitih parametara: temperature, vlage i svetlosti. Za određivanje koncentracije metilprednizolona, kao zbirne koncentracije metilprednizolon estara (17-hidrogen-sukcinata i 21-hidrogen-sukcinata) i slobodnog metilprednizolona, korišćena je metoda opisana u Američkoj farmakopeji. Za ispitivanje srodnih supstanci primenjena je HPLC metoda. Uočena su 4 degradaciona proizvoda. Dokazano je da povećanje temperature ima najveći značaj na proces degradacije i utiče na povećanje sadržaja nečistoća B, C i D, dok prisustvo svetlosti dovodi do povećanja sadržaja nečistoće A. Nečistoće B, C i D su identifikovane primenom masene i NMR spektroskopije. Sve tri nečistoće su identifikovane kao srodne supstance metilprednizolona.", publisher = "Srpsko hemijsko društvo, Beograd", journal = "Journal of the Serbian Chemical Society", title = "Methylprednisolone and its related substances in freeze-dried powders for injections, Metilprednizolon i njegove srodne supstance u liofilizatu za rastvor za injekcije", volume = "75", number = "10", pages = "1441-1452", doi = "10.2298/JSC100115087S" }
Solomun, L., Ibrić, S., Vajs, V., Vucković, I. M.,& Vujić, Z.. (2010). Methylprednisolone and its related substances in freeze-dried powders for injections. in Journal of the Serbian Chemical Society Srpsko hemijsko društvo, Beograd., 75(10), 1441-1452. https://doi.org/10.2298/JSC100115087S
Solomun L, Ibrić S, Vajs V, Vucković IM, Vujić Z. Methylprednisolone and its related substances in freeze-dried powders for injections. in Journal of the Serbian Chemical Society. 2010;75(10):1441-1452. doi:10.2298/JSC100115087S .
Solomun, Ljiljana, Ibrić, Svetlana, Vajs, Vlatka, Vucković, Ivan M., Vujić, Zorica, "Methylprednisolone and its related substances in freeze-dried powders for injections" in Journal of the Serbian Chemical Society, 75, no. 10 (2010):1441-1452, https://doi.org/10.2298/JSC100115087S . .