LC-MS/TOF and MSn studies on forced degradation behavior of flucloxacillin and development of a validated stability indicating LC method

Czasopismo : Acta Chromatographica
Tytuł artykułu : LC-MS/TOF and MSn studies on forced degradation behavior of flucloxacillin and development of a validated stability indicating LC method

Autorzy :
Komsta, Ł.
Medical University of Lublin Chair and Department of Medicinal Chemistry, Faculty of Pharmacy Jaczewskiego 4 20-090 Lublin Poland, lukasz.komsta@am.lublin.pl,
Gowin, E.
Medical University of Lublin Chair and Department of Medicinal Chemistry, Faculty of Pharmacy Jaczewskiego 4 20-090 Lublin Poland,
Djordjević Filijović, N.
Hemofarm AD Vrsac Serbia,
Pavlović, A.
Hemofarm AD Vrsac Serbia,
Nikolić, K.
University of Belgrade, Faculty of Pharmacy Department of Pharmaceutical Chemistry Vojvode Stepe 450 PO Box 146 11000 Belgrade Serbia,
Agbaba, D.
University of Belgrade, Faculty of Pharmacy Department of Pharmaceutical Chemistry Vojvode Stepe 450 PO Box 146 11000 Belgrade Serbia, danica@pharmacy.bg.ac.rs,
Sawant, S.
Sinhgad Technical Education Society’s Smt. Kashibai Navale College of Pharmacy, Kondhwa (Bk.) Pune 411 048 Maharashtra India, sawant99@rediffmail.com,
Barge, V.
PDEA’s Seth Govind Raghunath Sable College of Pharmacy Saswad, Tal-Purandar, Dist-Pune 412301 Maharashtra India,
Tiwari, R.
School of Pharmacy and Technology Department of Pharmaceutical Chemistry, SVKM’s NMIMS Management Shirpur Dist. Dhule 425405 Maharashtra India, ravisun4@rediffmail.com,
Bonde, C.
School of Pharmacy and Technology Department of Pharmaceutical Chemistry, SVKM’s NMIMS Management Shirpur Dist. Dhule 425405 Maharashtra India,
Bothara, K.
Sinhgad Institute of Pharmacy Department of Pharmaceutical Chemistry Narhe Road Pune 410041 Maharashtra India,
Abstrakty : The objective of the present investigation was to develop and validate a stability indicating liquid chromatography (LC) method which should possess potential to separate flucloxacillin as well as all the degradation products. Simultaneously, our aim was also to identify, separate, and characterize the major degradation product (DPs) of flucloxacillin, generated under various stress conditions. To achieve this objective, flucloxacillin was subjected to hydrolytic, oxidative, photolytic, and thermal stress as per International Conference on Harmonization (ICH) guidelines Q1A(R2). The drug was found to degrade in acidic, alkaline, neutral, and oxidative stress conditions and showed stable behavior in photolytic and thermal stress conditions. In total, seven degradation products were formed, which were separated on a C-18 column employing a gradient high-performance liquid chromatographic (HPLC) method. A complete mass fragmentation pathway of the drug was established with the help of multi-stage (MSn) and mass spectrometry/time of flight (MS/TOF) accurate mass studies. Then the stress samples were subjected to LC-MS/TOF studies, which provided the fragmentation pattern along with the accurate masses for a major degradation product. The entire mass spectral studies helped to identify the degradation product so as to propose its best possible structure. Finally the total information was used to establish the degradation pathway of the drug.

Słowa kluczowe : LC-MS/TOF, forced degradation, flucloxacillin,
Wydawnictwo : University of Silesia in Katowice
Rocznik : 2014
Numer : Vol. 26, no. 1
Strony : 43 – 55
Bibliografia : 1 B.C. McWhinney, S.C. Wallis, T. Hillister, J.A. Roberts, J. Lipman, and J.P. Ungerer, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 878, 2039 (2010)
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7 ICH, Validation of Analytical Procedures: Text and Methodology, Q2(R1), in: International Conference on Harmonization, IFPMA, Geneva, 2005
DOI :
Cytuj : Komsta, Ł. ,Gowin, E. ,Djordjević Filijović, N. ,Pavlović, A. ,Nikolić, K. ,Agbaba, D. ,Sawant, S. ,Barge, V. ,Tiwari, R. ,Bonde, C. ,Bothara, K. , LC-MS/TOF and MSn studies on forced degradation behavior of flucloxacillin and development of a validated stability indicating LC method. Acta Chromatographica Vol. 26, no. 1/2014
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