Login Register Cart 0
Generic placeholder image

Current Analytical Chemistry

Editor-in-Chief

ISSN (Print): 1573-4110
ISSN (Online): 1875-6727

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Investigation on the Stability of New Biologically Active Thiosemicarbazone- Derived Compounds by a Validated HPLC-PDA Method

Author(s): Daniela Secci, Marcello Locatelli*, Abuzar Kabir, Erika Salvatorelli, Giorgia Macedonio, Adriano Mollica and Simone Carradori*

Volume 15, Issue 3, 2019

Page: [313 - 320] Pages: 8

DOI: 10.2174/1573411014666180502105225

Price: $65

Abstract

Background: New Chemical Entities (NCEs) could be generally exposed to several stress conditions of hydrolysis, oxidation, photolysis and thermal degradation in order to better characterize the compounds and to know if the degradation processes lead to generate undesired (or toxic) products.

Objective: This paper reports the development and validation of an HPLC-PDA method for the qualiquantitative profiles determination and chemical-physical stability evaluation after forced decomposition studies of thiosemicarbazone-derived compounds endowed with interesting pharmacological activities.

Methods: All compounds and two possible degradation products were resolved by using a Grace® C-18 (ODS) column (250 mm × 4.6 mm; 5 mm particle size) in gradient elution mode. The chromatographic analysis was run in 28 min. The analytical method was correctly validated using weighted-matrix matched standard curves in the following ranges: 1-100 µg mL-1 for the lead compounds, and 0.1-8 μg mL-1 for the two possible degradation products showing a good correlation coefficients (≥0.9756). Precision and trueness comply with International Guidelines on method validation.

Results: The obtained results demonstrated an excellent stability of the thiosemicarbazone-derived products following the treatment with UV set at 254 nm and heat (at 80°C). In solution, however, the compounds showed different stability profiles.

Conclusion: The results obtained through the forced degradation studies provided important information not only for handling, formulation and storage of the substances, but also for the possible chemical changes in order to increase the stability. Given the importance of the non-conventional dosage forms, the stability of the substances was also analyzed in the presence of widely used surfactants.

Keywords: Forced decomposition studies, HPLC-PDA, method validation, new chemical entities, stability tests, thiosemicarbazone derivatives.

« Previous
Graphical Abstract

[1]
Tamizi, E.; Jouyban, A. Forced degradation studies of biopharmaceuticals: Selection of stress conditions. Eur. J. Pharm. Biopharm., 2016, 98, 26-46.
[2]
Blessy, M.; Ruchi, D.P.; Prajesh, N.P.; Agrawal, Y.K. Development of forced degradation and stability indicating studies of drugs. J. Pharm. Anal., 2014, 4(3), 159-165.
[3]
International Conference on Harmonisation of technical requirements for registration of pharmaceuticals for human use. Harmonised Tripartite Guideline: Validation of Analytical Procedures: Text and Methodology. ICH Q2(R1). 2005.
[4]
International Conference of Harmonisation of Technical Requirements for registration of pharmaceuticals for human use; "Stability testing: photostability testing of new drug substances and products. ICH Q1B. 1996.
[5]
International Conference of Harmonisation of Technical Requirements for registration of pharmaceuticals for human use; "Stability Testing of New Drug Substances and Products. ICH Q1A(R2). 2006.
[6]
Ngwa, G. Forced Degradation as an Integral Part of HPLC Stability-Indicating Method Development. Drug Delivery Technol., 2010, 10(5), 1-4.
[7]
Bakshi, M.; Ojha, T.; Singh, S. Validated specific HPLC methods for determination of prazosin, terazosin and doxazosin in the presence of degradation products formed under ICH-recommended stress conditions. J. Pharm. Biomed. Anal., 2004, 34(1), 19-26.
[8]
Kovaříkovà, P.; Mokŕy, M.; Klimes, J.; Vávrová, K. HPLC study on stability of pyridoxal isonicotinoyl hydrazone. J. Pharm. Biomed. Anal., 2006, 40(1), 105-112.
[9]
Kovaříkovà, P.; Klimeš, J.; Dohnal, J.; Tisovská, L. HPLC study of glimepiride under hydrolytic stress conditions. J. Pharm. Biomed. Anal., 2004, 36(1), 205-209.
[10]
Sharma, S.; Sharma, M.C.; Chaturvedi, S.C. Study of stressed degradation behavior of pioglitazone hydrochloride in bulk and pharmaceutical formulation by HPLC assay method. J. Optoelectronics Biomed. Mat., 2010, 1(1), 17-24.
[11]
Sawant, S.D.; Barge, V.U. Identification and characterization of forced degradation products of paliperidone using LC-APCI-Ion Trap-MS. J. Pharm. Res., 2013, 6(1), 39-47.
[12]
Doomkaew, A.; Prutthiwanasan, B.; Suntornsuk, L. Stability indicating MEKC method for the determination of gliclazide and its specified impurities. J. Pharm. Biomed. Anal., 2015, 102, 119-128.
[13]
Michail, K.; Daabees, H.M.; Beltagy, Y.; Abdel-Khalek, M.; Khamis, M.M. Stress Degradation Assessment of Lamotrigine Using a Validated Stability-Indicating HPTLC Method. J. Chem., 2013, 2013, 1-6.
[14]
Gopu, C.L.; Thomas, S.; Paradkar, A.R.; Mahadik, K.R. A validated stability indicating HPTLC method for determination of nitazoxamide. J. Sci. Ind. Res., 2007, 66, 141-145.
[15]
Stariat, J.; Kovaříkovà, P.; Klimes, J.; Lovejoy, D.B.; Kalinowski, D.S. Richardson, De R. HPLC methods for determination of two novel thiosemicarbazone anti-cancer drugs (N4mT and Dp44mT) in plasma and their application to in vitro plasma stability of these agents. J. Chromatogr. B., 2009, 877(3), 316-322.
[16]
Mrkvičková, Z.; Kovaříkovà, P.; Klimes, J.; Kalinowski, D.; Richardson, D.R. Development and validation of HPLC-DAD methods for the analysis of two novel iron chelators with potent anti-cancer activity. J. Pharm. Biomed. Anal., 2007, 43(4), 1343-1351.
[17]
Kovaříkovà, P.; Mrkvičková, Z.; Klimeš, J. Investigation of the stability of aromatic hydrazones in plasma and related biological material. J. Pharm. Biomed. Anal., 2008, 47(2), 360-370.
[18]
Hassan, A.A.; Shawky, A.M.; Shehatta, H.S. Chemistry and heterocyclization of thiosemicarbazones. J. Het. Chem., 2012, 49(1), 21-37.
[19]
Campestre, C.; Locatelli, M.; Guglielmi, P.; De Luca, E.; Bellagamba, G.; Menta, S.; Zengin, G.; Celia, C.; Di Marzio, L.; Carradori, S. Analysis of imidazoles and triazoles in biological samples after MicroExtraction by packed sorbent. J. Enz Inhibit. Med. Chem., 2017, 32(1), 1053-1063.
[20]
Locatelli, M.; Ciavarella, M.T.; Paolino, D.; Celia, C.; Fiscarelli, E.; Ricciotti, G.; Pompilio, A.; Di Bonaventura, G.; Grande, R.; Zengin, G.; Di Marzio, L. Determination of ciprofloxacin and levofloxacin in human sputum collected from cystic fibrosis patients using microextraction by packed sorbent-high performance liquid chromatography photodiode array detector. J. Chromatogr. A, 2015, 1419, 58-66.
[21]
Locatelli, M.; Cifelli, R.; Di Legge, C.; Barbacane, R.C.; Costa, N.; Fresta, M.; Celia, C.; Capolupo, C.; Di Marzio, L. Simultaneous determination of eperisone hydrochloride and paracetamol in mouse plasma by high performance liquid chromatography-photodiode array detector. J. Chromatogr. A, 2015, 1388, 79-86.
[22]
Kabir, A.; Furton, K.G.; Tinari, N.; Grossi, L.; Innosa, D.; Macerola, D.; Tartaglia, A.; Di Donato, V.; D’Ovidio, C.; Locatelli, M. Fabric phase sorptive extraction-high performance liquid chromatography-photo diode array detection method for simultaneous monitoring of three inflammatory bowel disease treatment drugs in whole blood, plasma and urine. J. Chromatogr. B., 2018, 1084, 53-63.
[23]
Locatelli, M.; Kabir, A.; Innosa, D.; Lopatriello, T.; Furton, K.G. A fabric phase sorptive extraction-High performance liquid chromatography-Photo diode array detection method for the determination of twelve azole antimicrobial drug residues in human plasma and urine. J. Chromatogr. B., 2017, 1040, 192-198.
[24]
De Monte, C.; Carradori, S.; Secci, D.; D’Ascenzio, M.; Guglielmi, P.; Mollica, A.; Morrone, S.; Scarpa, S.; Aglianò, A.M.; Giantulli, S.; Silvestri, I. Synthesis and pharmacological screening of a large library of 1,3,4-thiadiazolines as innovative therapeutic tools for the treatment of prostate cancer and melanoma. Eur. J. Med. Chem., 2015, 105, 245-262.
[25]
Carradori, S.; Secci, D.; D’Ascenzio, M.; Chimenti, P.; Bolasco, A. Microwave and ultrasound-assisted synthesis of thiosemicarbazones and their corresponding (4,5-substituted-thiazol-2-yl)hydrazines. J. Heterocyclic. Chem., 2014, 51(6), 1856-1861.
[26]
D’Ascenzio, M.; Bizzarri, B.; De Monte, C.; Carradori, S.; Bolasco, A.; Secci, D.; Rivanera, D.; Faulhaber, N.; Bordón, C.; Jones-Brando, L. Design, synthesis and biological characterization of thiazolidin-4-one derivatives as promising inhibitors of Toxoplasma gondii. Eur. J. Med. Chem., 2014, 86, 17-30.
[27]
CDER and CVM Guidance for Industry, Bioanalytical Method Validation. Food and Drug Administration, (Accessed May 2001). Available at: http://www.fda.gov\cder\guidance\4252fnl.pdf.
[28]
Taverniers, I.; Van Bockstaele, E.; De Loose, M. Trends in quality in the analytical laboratory. II. Analytical method validation and quality assurance. Trends Anal. Chem., 2004, 23(8), 535-552.
[29]
Rinaldi, F.; Hanieh, P.N.; Longhi, C.; Carradori, S.; Secci, D.; Zengin, G.; Ammendolia, M.G.; Mattia, E.; Del Favero, E.; Marianecci, C.; Carafa, M. Neem oil nanoemulsions: characterisation and antioxidant activity. J. Enzyme Inhib. Med. Chem., 2017, 32, 1265-1273.

Rights & Permissions Print Cite
Article Metrics
44
3
1
© 2024 Bentham Science Publishers | Privacy Policy