PIPERIDINIUM 2-((5-(FURAN-2-YL)-4-PHENYL-4H-1,2,4-TRIAZOL)-3- YL) ACETATE FORCED DEGRADATION STUDY

Yıl 2019, , 117 - 134, 01.06.2019

Borys Varynskyi

https://doi.org/10.33483/jfpau.480073

Öz

Objective: Aim of the research to make forced degradation study of piperidinium
2-((5- (furan-2-yl)-4-phenyl-4H-1,2,4-triazol-3-yl) acetate in active pharmaceutical
ingredient (API), 0.1% solution and 1% solution for injection. Influence of
the sodium hydroxide, hydrochloride acid, 3% Н₂О₂,
temperature, UV radiation on piperidine 2-((5-(furan-2-yl)
-4-phenyl-4H-1,2,4-triazol-3-yl) acetate substance, 0.1% solution and 1%
solution for injections was studied. Material and method: Agilent 1260 Infinity HPLC System. Agilent single-quadrupole mass spectrometer 6120. Result
and discussion: Dependence of the quantitative content of the piperidinium
2-((5-(furan-2-yl)-4-phenyl-4H-1,2,4-triazol-3-yl) acetate from exposition time
was determined. The composition of impurities formed under the action of an oxidizer was
established (3%Н₂О₂). This is sulfoxide and sulfone
corresponding to the API. The composition of impurities which were formed under the influence of UV
radiation was proposed.

Anahtar Kelimeler

ESI mass spectrometry, forced degradation stuy, high pressure liquid chromatography, triazoles

Teşekkür

We acknowledge complete support of the Zaporozhye State Medical University. We thank rector of Zaporozhye State Medical University Prof. Yu. M. Kolesnyk for his help and support.

PİPERİDİNYUM 2-((5-(FURAN-2-İL)-4-FENİL-4H-1,2,4-TRİAZOL)-3-İL) ASETATIN ZORLANMIŞ BOZUNMA ÇALIŞMASI

Öz

        Amaç: Bu araştırmanın amacı; aktif farmasötik içerikteki (API) 2-((5-(furan-2-İl)-4-fenİl-4H-1,2,4-trİazol)-3-İl)
asetat maddesinin % 0.1 çözeltisinin ve enjeksiyonluk % 1 çözeltisinin
zorlanmış bozunmasının incelenmesidir. Çalışma, sodyum hidroksit, hidroklorik
asit,% 3 H₂O₂, sıcaklık ve UV radyasyonunda bulunan piperidinyum
2–((5-(furan-2-il)-4-fenil-4H-1,2,4-triazol)-3-il) asetatın % 0.1 çözelti ve
enjeksiyonluk % 1'lik çözeltisinde gerçekleştirilmiştir.

       
Gereç ve Yöntem: Agilent 1260 Infinity HPLC Sistemi. Agilent dört kutuplu kütle
spektrometresi 6120.

        Sonuç ve Tartışma: Piperidinyum 2-((5-(furan-2-il)-4-fenil-4H-1,2,4-triazol)-3-il)
asetatın kantitatif içeriğinin, maruz kalma süresine bağlı olduğu
belirlenmiştir. Oksitleyicinin (% 3 Н₂О₂) etkisi altında
oluşan bozunma ürünlerinin bileşimi gösterilmiştir. UV radyasyonunun etkisi altında oluşan bozunma
ürünlerinin bileşimi önerilmiştir.    

Anahtar Kelimeler

ESI kütle spektrometresi, triazoller, yüksek basınçlı sıvı kromatografisi, zorlanmış bozunma çalışması

Kaynakça

• Sehrawat, R., Maithani, M., Singh, R. (2010). Regulatory Aspects in Development of Stability-Indicating Methods: A Review. Chromatographia, 72 (1/2), 1–6.
• Blessy, M, Ruchi, D. P., Prajesh, N. Pr., Agrawal Y.K. (2014). Development of forced degradation and stability indicating studies of drugs—A review. Journal of Pharmaceutical Analysis; 4(3), 159–165.
• Klick, S., Muijselaar, P. G., Waterval J., Eichinger, Th., Korn, C., Gerding Th. K., Debets Al. J., Van de Griend C. S., Van den Beld C., Somsen G. W. and De Jong G. J. (2005). Stress Testing of Drug Substances and Drug Products. Pharmaceutical Technology, FEBRUARY; 48–66.
• Chakravarthy, V. A., Sailaja, B. B. V., Kumar A. P. (2015). Stability-Indicating RP-HPLC Method for Simultaneous Estimation of Enrofloxacin and Its Degradation Products in Tablet Dosage Forms. Journal of Analytical Methods in Chemistry, 1 – 11
• Ahirrao, V. K., Patil, C. S., Bembalkar, S. R., Katariya, M. V., Sonnekar, V. S., Marathe, R. P., Nawale, R. B., Pawar, R. P. (2012). Stress degradation studies of dronedarone in pharmaceutical dosage form by a validated stability-indicating LC method. Journal of the Chilean Chemical Society,57(3); 1272 – 1276.
• Patel, J. K., Patel, N. K. (2014). Stability-Indicating RP-HPLC Method for the Determination of Ambrisentan and Tadalafil in Pharmaceutical Dosage Form. Scientia Pharmaceutica, 82, 749–763
• Parchenko, V. (2006). Synthesis, physicochemical and biological properties of derivatives of 1,2,4-triazoles-3-thione containing core furan. Candidate of PharmSci thesis, Zaporozhye State Medical University, Zaporozhye, 208 p.
• Parchenko, V. (2014). Synthesis, transformation, physico-chemical and biological properties in a number of 5-furyl-substituted 1,2,4-triazole-3-thiones. Dr. Pharmacist Sciences thesis, Zaporozhye State Medical University, Zaporozhye, 460 p.
• Tietze, L.F., Eicher, Th. (1991). Reaktionen und Synthesen im organisch‐chemischen Praktikum und Forschungslaboratorium. 2. Aufl., Georg Thieme Verlag, Stuttgart – New York. DM 68, 672 S.
• Varynskyi, B. O. (2016). Optimization of the detection conditions for the series of 1,2,4-triazole-3-thiones for FIA-ESI-MS and HPLC-ESI-MS. NEWS OF PHARMACY, 1(85), 7-11.