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.
TY - 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 . .
