Reverse-Phase Chromatographic Determination and Intrinsic Stability Behavior of 5-[(4-Chlorophenoxy)Methyl]-1,3,4-Oxadiazole-2-Thiol

Open access

Abstract

The study describes the development and preliminary validation of a simple reverse-phase chromatographic method for determination of a novel drug candidate, 5-[(4-chlorophenoxy) methyl]-1,3,4-oxadiazole-2-thiol (OXCPM), in bulk and stressed solution, in order to find out the intrinsic stability behavior of the compound. Isocratic elution was carried out at a flow rate of 1.0 mL min-1 through a Promosil C18 column maintained at 25 °C, using the mobile phase comprising acetonitrile and aqueous o-H3PO4 (pH 2.67) (1:1, V/V). Detection was performed at 258 nm. The response of the detector was linear in a concentration range of 1.25-50.00 μg mL-1 with the correlation coefficient of 0.9996 ± 0.0001. Cumulative intra-day, inter-day and inter-instrument accuracy (99.5 ± 1.0, 100.2 ± 1.0 and 100.3 ± 0.4 %, resp.) with RSD less than 5 % indicated that the method was accurate and precise. The resolution and selectivity factor (>2 and >1, resp.), particularly in copper metal- and dry-heat-stress solutions, depicted the selectivity of the method. OXCPM remained stable under hydrolytic (acidic and neutral pH, ≤ 37 °C), photolytic and moist heat stress conditions. Under alkaline conditions (hydrolytic and photolytic), polar products were formed that eluted very fast through the column (tR < 3.75 min). At room temperature, the compound was susceptible to oxidation by hydrogen peroxide and transition metals. The ionogram of most of the stress solutions indicated the presence of a product having m/z 256, which might be a result of N- or Smethylation or -SH oxidation. The results of the study indicate that the method is selective, sensitive and suitable to be used for determination of OXCPM in bulk and under stress conditions.

1. S. Z. Siddiqui, M. A. Abbasi, A. Rehman, M. Irshad, M. Ashraf, I. Ahmad, M. A. Lodhi, B. Mirza, H. Ismail, M. N. Akhtar and B. Shahzad, Synthesis, pharmacological evaluation, molecular docking and cytotoxicity studies on some N-substituted 5-[(4-chlorophenoxy)methyl]1,3,4-oxadiazole- 2yl-2-sulfanyl acetamides, Indo. Am. J. Pharm. Res. 4 (2014) 3603-3617.

2. C. S. de Oliveira, B. F. Lira, J. M. Barbosa-Filho, J. G. F. Lorenzo and P. F. de Athayde-Filho, Synthetic approaches and pharmacological activity of 1,3,4-oxadiazoles: A review of the literature from 2000-2012, Molecules 17 (2012) 10192-10231; https//doi.org/10.3390/molecules170910192

3. A. Savarino, A historical sketch of the discovery and development of HIV-1 integrase inhibitors, Expert Opin. Investig. Drugs 15 (2004) 1507-1522; https//doi.org/10.1517/13543784.15.12.1507

4. E. D. Chrysina, M. N. Kosmopoulou, C. Tiraidis, R. Kardakaris, N. Bischler, D. D. Leonidas, Z. Hadady, L. Somsak, T. Docsa, P. Gergely and N. G. Oikonomakos, Kinetic and crystallographic studies on 2-(β-D-glucopyranosyl)-5-methyl-1,3,4-oxadiazole, -benzothiazole, and -benzimidazole, inhibitors of muscle glycogen phosphorylase b. Evidence for a new binding site, Protein Sci. 14 (2005) 873-888; https//doi.org/10.1110/ps.041216105

5. N. D. James and J. W. Growcott, Zibotentan, Drugs Fut. 34 (2009) 624-633; https//doi.org/10.1358/ dof.2009.034.08.1400202

6. R. R. Somani and P. Y. Shirodkar, Oxadiazole: A biologically important heterocycle, Pharma Chem. 1 (2009) 130-140.

7. N. Shehzadi, K. Hussain, M. Islam, N. I. Bukhari, M. T. Khan, M. Salman, S. Z. Siddiqui, A. Rehman and M. A. Abbasi, In silico drug-qualifying parameters of 5-[(4-chlorophenoxy)methyl]-1,3,4- oxadiazole-2-thiol, Lat. Am. J. Pharm. 35 (2016) 1991-1997.

8. Center for Drug Evaluation and Research (CDER), Reviewer Guidance: Validation of Chromatographic Methods, Rockville, MD, 1994; http://www.fda.gov/downloads/Drugs/.../Guidances/UCM134409.pdf; last access date March 10, 2018.

9. Food and Drug Administration (FDA), Guidance for Industry, Analytical Procedures and Methods Validation: Chemistry, Manufacturing and Controls Documentation, in Draft Guidance, Rockville, MD, 2000.

10. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Validation of Analytical Procedures: Text and Methodology Q2(R1), Current Step 4 version, Nov. 1996, Geneva, Nov. 2005; http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1_Guideline.pdf; last access date March 10, 2018.

11. S. Singh and M. Bakshi, Stress test to determine inherent stability of drugs, Pharm. Technol. 4 (2000) 1-14.

12. M. Bakshi, B. Singh, A. Singh and S. Singh, The ICH guidance in practice: stress degradation studies on ornidazole and development of a validated stability-indicating assay, J. Pharm. Biomed. Anal. 26 (2001) 891-897; https://doi.org/10.1016/S0731-7085(01)00475-7

13. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, ICH Harmonized Tripartite Guideline, Stability Testing of New Drug Substances and Products ICH Q1A (R2), Current Step 4 version, Sep 1992, Geneva, Feb 2003; https:// www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q1A_R2/Step4/Q1A_R2__Guideline.pdf; last access date March 9, 2018.

14. K. K. Hotha, S. P. K. Reddy, V. K. Raju and L. K. Ravindranath, Forced degradation studies: Practical approach-overview of regulatory guidance and literature for the drug products and drug substances, Int. Res. J. Pharm. 4 (2013) 78-85.

15. J. J. Pignatello, Dark and photoassisted iron(3+)-catalyzed degradation of chlorophenoxy herbicides by hydrogen peroxide, Environ. Sci. Technol. 26 (1992) 944-951; https//doi.org/10.1021/ es00029a012

16. Z. D. Okram, B. Kanakapura, R. P. Jagannathamurthy and V. K. Basavaiah, Development of a simple UV-spectrophotometric method for the determination of lansoprazole and study of its degradation profile, Quím. Nova 35 (2012) 386-391; https://doi.org/10.1590/S0100-40422012000200027

17. K. L. Maier, E. Matejkva, H. Hinze, L. Leuschel, H. Weber and I. Beck-Speier, Different selectivities of oxidants during oxidation of methionine residues in the α-1-proteinase inhibitor, FEBS Lett. 250 (1989) 221-226.

18. C. M. Maciolek, B. Ma, K. Menzel, S. Laliberte, K. Bateman, P. Krolikowski and C. R. Gibson, Novel cytochrome P450-mediated ring opening of the 1,3,4-oxadiazole in setileuton, a 5-lipoxygenase inhibitor, Drug Metab. Dispos. 39 (2011) 763-770; https://doi.org/10.1124/dmd.110.037366

19. A. Corma, T. Ródenas and M. J. Sabater, Aerobic oxidation of thiols to disulfides by heterogeneous gold catalysts, Chem. Sci. 3 (2012) 398-404; http://doi.org/10.1039/C1SC00466B

20. R. Kumar and S. L. Khokara, Chemistry and common synthetic route of 1,3,4-oxadiazole: an important heterocyclic moiety in medicinal chemistry, Int. J. Inst. Pharm. Life Sci. 2 (2005) 224-230.

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

Journal Information


IMPACT FACTOR 2017: 1.071
5-year IMPACT FACTOR: 1.623

CiteScore 2017: 1.46

SCImago Journal Rank (SJR) 2017: 0.362
Source Normalized Impact per Paper (SNIP) 2017: 0.642

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 56 56 56
PDF Downloads 21 21 21