Research Article
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Development and validation of an RP-HPLC method for simultaneous determination of curcumin and metronidazole in combined dosage form

Year 2022, Volume: 52 Issue: 3, 250 - 257, 30.12.2022

Leyla Beba Pojarani E. Vildan Burgaz Esra Baloglu

https://doi.org/10.26650/IstanbulJPharm.2022.1005453

Abstract

Background and Aims: The present study aimed to develop and validate a simple reverse phase-high pressure liquid chro- matography (RP-HPLC) method for simultaneous determination of natural compound curcumin and metronidazole in bulk and its combined dosage form.
Methods: In situ gel formulation containing curcumin and metronidazole was prepared as a model combined system. The chromatographic separation was accomplished isocratically on Eclipse XDB-C18 (150 mm x 4.6 mm, 5 μm particle size) col- umn using UV-detection at 254 nm. The optimized mobile phase contained a mixture of Phosphate Buffer pH4.5-Acetonitrile (50:50, v/v), and the flow rate was set to 1.0 mL/min with 10 μL injection volume. The method was validated in compliance with International Council for Harmonisation (ICH) standards, and it was successfully used for quality control assays for their combined drug product
Results: The results for retention times were 8.60 and 1.40 min for curcumin and metronidazole, respectively. The method indicated linear responses within the concentration ranges of 3.0-80 and 4.8-128 μg/mL with LOD values of 0.62; 1.03 μg/mL and LOQ values of 1.88; 3.13 μg/mL for curcumin and metronidazole, respectively. Precision results were within acceptable limits (RSD<2%), and the determination of the two active substances was not interfered with by any formulation components. Conclusion: The proposed validated RP-HPLC method was successfully applied to determine the total contents of curcumin and metronidazole in situ gel formulation. The validation results showed that the proposed method was simple, specific, and precise, and that it could be used for routine quality control for their combined pharmaceutical application.

Keywords

Curcumin Metronidazole Simultaneous-quantification HPLC method development

Supporting Institution

N/A

Project Number

N/A

Thanks

N/A

References

  • Baloglu, E., Karavana, S. Y., Senyigit, Z. A., & Guneri, T. (2011a). Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharmaceutical development and technology, 16(6), 627-636. doi: 10.3109/10837450.2010.508074.
  • Baloglu, E., Karavana, S. Y., Senyigit, Z. A., Hilmioglu-Polat, S., Metin, D. Y., Zekioglu, O., ... & Jones, D. S. (2011b). In-situ gel formulations of econazole nitrate: preparation and in-vitro and in-vivo evalua- tion. Journal of Pharmacy and Pharmacology, 63(10), 1274-1282. doi: 10.1111/j.2042-7158.2011.01315.x.
  • Basnet, P., & Skalko-Basnet, N. (2011). Curcumin: an anti-inflam- matory molecule from a curry spice on the path to cancer treatment. Molecules, 16(6), 4567-4598. doi: 10.3390/mole- cules16064567.
  • Berginc, K., Škalko-Basnet, N., Basnet, P., & Kristl, A. (2012). Devel- opment and evaluation of an in vitro vaginal model for assess- ment of drug’s biopharmaceutical properties: Curcumin. AAPS PharmSciTech, 13(4), 1045-1053. doi: 10.1208/s12249-012-9837-9.
  • Çelebier, M., Kaynak, M. S., Altınöz, S., & Sahin, S. (2010). HPLC method development for the simultaneous analysis of amlodip- ine and valsartan in combined dosage forms and in vitro dissolu- tion studies. Brazilian Journal of Pharmaceutical Sciences, 46, 761- 768. doi: 10.1590/S1984-82502010000400018.
  • Chanda, S., & Rakholiya, K. (2011). Combination therapy: Syner- gism between natural plant extracts and antibiotics against in- fectious diseases. In A. Méndez-Vilas (Ed.), Science against micro- bial pathogens: communicating current research and technological advances (pp. 520-529). Formatex, Spain.
  • Chaudhary, H., Kohli, K., Amin, S., Arora, S., Kumar, V., Rathee, S., & Rathee, P. (2012). Development and validation of RP-HPLC method for simultaneous estimation of diclofenac diethyl- amine and curcumin in transdermal gels. Journal of Liquid Chromatography & Related Technologies, 35(1), 174-187. doi: 10.1080/10826076.2011.597068.
  • Cheraghipour, K., Marzban, A., Ezatpour, B., Khanizadeh, S., & Koshki, J. (2018). Antiparasitic properties of curcumin: A re- view. AIMS Agriculture and Food, 3(4), 561–578. doi: 10.3934/ AGRFOOD.2018.4.561.
  • Edsman, K., Carlfors, J., & Petersson, R. (1998). Rheological evalua- tion of poloxamer as an in situ gel for ophthalmic use. European Journal of Pharmaceutical Sciences, 6(2), 105-112. doi: 10.1016/ S0928-0987(97)00075-4.
  • Ejim, L., Farha, M. A., Falconer, S. B., Wildenhain, J., Coombes, B. K., Tyers, M., Brown, E.D., & Wright, G. D. (2011). Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial effi- cacy. Nature Chemical Biology, 7(6), 348-350. doi: 10.1038/nchem- bio.559.
  • Galmier, M. J., Frasey, A. M., Bastide, M., Beyssac, E., Petit, J., Aiache, J. M., & Lartigue-Mattei, C. (1998). Simple and sensitive method for determination of metronidazole in human serum by high- performance liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications, 720(1-2), 239-243. doi: 10.1016/S0378-4347(98)00443-5.
  • Garala, K., Joshi, P., Shah, M., Ramkishan, A., & Patel, J. (2013). For- mulation and evaluation of periodontal in situ gel. International journal of pharmaceutical investigation, 3(1), 29. doi: 10.4103/2230- 973x.108961.
  • Giuliano, E., Paolino, D., Fresta, M., & Cosco, D. (2018). Mucosal ap- plications of poloxamer 407-based hydrogels: An overview. Phar- maceutics, 10(3), 159. doi: 10.3390/pharmaceutics10030159.
  • Held, R. B. (1987). Rural resource management. In Cloke, P.J., & Park, C.C. London: Croom Helm, 1985. 473.
  • Ibrahim, S.A., Ismail, S., Fetih, G., Shaaban, O., Hassanein, K., & Ab- dellah, N. H. (2012). Development and characterization of ther- mosensitive pluronic-based metronidazole in situ gelling formu- lations for vaginal application. Acta pharmaceutica, 62(1), 59-70. doi: 10.2478/v10007-012-0009-y.
  • ICH. (2005). ICH Topic Q2 (R1) Validation of Analytical Procedures: Text and Methodology. International Conference on Harmoniza- tion 1994 (p.17).
  • Isacchi, B., Bergonzi, M. C., Grazioso, M., Righeschi, C., Pietretti, A., Severini, C., & Bilia, A. R. (2012). Artemisinin and artemisinin plus curcumin liposomal formulations: enhanced antimalarial efficacy against Plasmodium berghei-infected mice. European Journal of Pharmaceutics and Biopharmaceutics, 80(3), 528-534. doi: 10.1016/j.ejpb.2011.11.015.
  • Jain, A., Doppalapudi, S., Domb, A. J., & Khan, W. (2016). Tacroli- mus and curcumin co-loaded liposphere gel: Synergistic com- bination towards management of psoriasis. Journal of Controlled Release, 243, 132-145. doi: 10.1016/j.jconrel.2016.10.004.
  • Jangle, R. D., & Thorat, B. N. (2013). Reversed-phase high- performance liquid chromatography method for analysis of curcuminoids and curcuminoid-loaded liposome formula- tion. Indian Journal of Pharmaceutical Sciences, 75(1), 60-66. doi: 10.4103/0250-474X.113555.
  • Jayaprakasha, G. K., Jagan Mohan Rao, L., & Sakariah, K. K. (2002). Improved HPLC method for the determination of curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Journal of Agricultural and Food Chemistry, 50(13), 3668-3672. doi: 10.1021/ jf025506a.
  • Ji, L., Jiang, Y., Wen, J., Fan, G., Wu, Y., & Zhang, C. (2009). A rapid and simple HPLC method for the determination of curcumin in rat plasma: assay development, validation and application to a pharmacokinetic study of curcumin liposome. Biomedical Chro- matography, 23(11), 1201-1207. doi: 10.1002/bmc.1244.
  • Lakshmi, Y. S., Kumar, P., Kishore, G., Bhaskar, C., & Kondapi, A. K. (2016). Triple combination MPT vaginal microbicide using cur- cumin and efavirenz loaded lactoferrin nanoparticles. Scientific reports, 6(1), 1-13. doi: 10.1038/srep25479.
  • Mun, S. H., Joung, D. K., Kim, Y. S., Kang, O. H., Kim, S. B., Seo, Y. S., ... & Kwon, D. Y. (2013). Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus. Phytomedi- cine, 20(8-9), 714-718. doi: 10.1016/J.PHYMED.2013.02.006.
  • Rangel-Castañeda, I. A., Hernández-Hernández, J. M., Pérez-Ran- gel, A., González-Pozos, S., Carranza-Rosales, P., Charles-Niño, C. L., ... & Castillo-Romero, A. (2018). Amoebicidal activity of curcumin on Entamoeba histolytica trophozoites. Journal of Pharmacy and Pharmacology, 70(3), 426-433. doi: 10.1111/jphp.12867.
  • Sasidharan, N. K., Sreekala, S. R., Jacob, J., & Nambisan, B. (2014). In vitro synergistic effect of curcumin in combination with third generation cephalosporins against bacteria associated with infectious diarrhea. BioMed Research International, 2014. doi: 10.1155/2014/561456.
  • Singh, S., & Giri, S. (2013). Curcumin protects oxidative stress and DNA damage induced by metronidazole and gamma radiation in vivo. Paper presented at the: Environmental Mutagen Society of India and national conference on current perspectives on en- vironmental mutagenesis and human health, Mumbai (India), Abstract retrieved from https://www.osti.gov/etdeweb/bib- lio/22082419
  • Teow, S. Y., & Ali, S. A. (2015). Synergistic antibacterial activity of Curcumin with antibiotics against Staphylococcus aureus. Paki- stan Journal of Pharmaceutical Sciences, 28(6), 2109-2114.
  • Topal, M., Şenel, G. U., Arslan Topal, E. I., & Öbek, E. (2015). Antibiyo-tikler ve kullanım alanları. Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi, 31(3), 121-127.
  • USP, (2015). U.S. Pharmacopoeia-national formulary [USP 38 NF 33]. Rockville, Md United States Pharmacopeial Convention. volume 1.
  • Venkateshwaran, T. G., & Stewart, J. T. (1995). Determination of metronidazole in vaginal tissue by high-performance liquid chro- matography using solid-phase extraction. Journal of Chromatog- raphy B: Biomedical Sciences and Applications, 672(2), 300-304. doi: 10.1016/0378-4347(95)00217-7.
  • Wachter, B., Syrowatka, M., Obwaller, A., & Walochnik, J. (2014). In vitro efficacy of curcumin on Trichomonas vaginalis. Wiener klinische Wochenschrift, 126(1), 32-36. doi: 10.1007/s00508-014- 0522-8.
  • Yu, T., Malcolm, K., Woolfson, D., Jones, D. S., & Andrews, G. P. (2011). Vaginal gel drug delivery systems: understanding rheo- logical characteristics and performance. Expert Opinion on Drug Delivery, 8(10), 1309-1322. doi: 10.1517/17425247.2011.600119.
  • Yuan, Y., Cui, Y., Zhang, L., Zhu, H. P., Guo, Y. S., Zhong, B., ... & Chen, L. (2012). Thermosensitive and mucoadhesive in situ gel based on poloxamer as new carrier for rectal administration of nimesu- lide. International Journal of Pharmaceutics, 430(1-2), 114-119. doi: 10.1016/j.ijpharm.2012.03.054.

Year 2022, Volume: 52 Issue: 3, 250 - 257, 30.12.2022

Leyla Beba Pojarani E. Vildan Burgaz Esra Baloglu

https://doi.org/10.26650/IstanbulJPharm.2022.1005453

Abstract

Project Number

N/A

References

  • Baloglu, E., Karavana, S. Y., Senyigit, Z. A., & Guneri, T. (2011a). Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharmaceutical development and technology, 16(6), 627-636. doi: 10.3109/10837450.2010.508074.
  • Baloglu, E., Karavana, S. Y., Senyigit, Z. A., Hilmioglu-Polat, S., Metin, D. Y., Zekioglu, O., ... & Jones, D. S. (2011b). In-situ gel formulations of econazole nitrate: preparation and in-vitro and in-vivo evalua- tion. Journal of Pharmacy and Pharmacology, 63(10), 1274-1282. doi: 10.1111/j.2042-7158.2011.01315.x.
  • Basnet, P., & Skalko-Basnet, N. (2011). Curcumin: an anti-inflam- matory molecule from a curry spice on the path to cancer treatment. Molecules, 16(6), 4567-4598. doi: 10.3390/mole- cules16064567.
  • Berginc, K., Škalko-Basnet, N., Basnet, P., & Kristl, A. (2012). Devel- opment and evaluation of an in vitro vaginal model for assess- ment of drug’s biopharmaceutical properties: Curcumin. AAPS PharmSciTech, 13(4), 1045-1053. doi: 10.1208/s12249-012-9837-9.
  • Çelebier, M., Kaynak, M. S., Altınöz, S., & Sahin, S. (2010). HPLC method development for the simultaneous analysis of amlodip- ine and valsartan in combined dosage forms and in vitro dissolu- tion studies. Brazilian Journal of Pharmaceutical Sciences, 46, 761- 768. doi: 10.1590/S1984-82502010000400018.
  • Chanda, S., & Rakholiya, K. (2011). Combination therapy: Syner- gism between natural plant extracts and antibiotics against in- fectious diseases. In A. Méndez-Vilas (Ed.), Science against micro- bial pathogens: communicating current research and technological advances (pp. 520-529). Formatex, Spain.
  • Chaudhary, H., Kohli, K., Amin, S., Arora, S., Kumar, V., Rathee, S., & Rathee, P. (2012). Development and validation of RP-HPLC method for simultaneous estimation of diclofenac diethyl- amine and curcumin in transdermal gels. Journal of Liquid Chromatography & Related Technologies, 35(1), 174-187. doi: 10.1080/10826076.2011.597068.
  • Cheraghipour, K., Marzban, A., Ezatpour, B., Khanizadeh, S., & Koshki, J. (2018). Antiparasitic properties of curcumin: A re- view. AIMS Agriculture and Food, 3(4), 561–578. doi: 10.3934/ AGRFOOD.2018.4.561.
  • Edsman, K., Carlfors, J., & Petersson, R. (1998). Rheological evalua- tion of poloxamer as an in situ gel for ophthalmic use. European Journal of Pharmaceutical Sciences, 6(2), 105-112. doi: 10.1016/ S0928-0987(97)00075-4.
  • Ejim, L., Farha, M. A., Falconer, S. B., Wildenhain, J., Coombes, B. K., Tyers, M., Brown, E.D., & Wright, G. D. (2011). Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial effi- cacy. Nature Chemical Biology, 7(6), 348-350. doi: 10.1038/nchem- bio.559.
  • Galmier, M. J., Frasey, A. M., Bastide, M., Beyssac, E., Petit, J., Aiache, J. M., & Lartigue-Mattei, C. (1998). Simple and sensitive method for determination of metronidazole in human serum by high- performance liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications, 720(1-2), 239-243. doi: 10.1016/S0378-4347(98)00443-5.
  • Garala, K., Joshi, P., Shah, M., Ramkishan, A., & Patel, J. (2013). For- mulation and evaluation of periodontal in situ gel. International journal of pharmaceutical investigation, 3(1), 29. doi: 10.4103/2230- 973x.108961.
  • Giuliano, E., Paolino, D., Fresta, M., & Cosco, D. (2018). Mucosal ap- plications of poloxamer 407-based hydrogels: An overview. Phar- maceutics, 10(3), 159. doi: 10.3390/pharmaceutics10030159.
  • Held, R. B. (1987). Rural resource management. In Cloke, P.J., & Park, C.C. London: Croom Helm, 1985. 473.
  • Ibrahim, S.A., Ismail, S., Fetih, G., Shaaban, O., Hassanein, K., & Ab- dellah, N. H. (2012). Development and characterization of ther- mosensitive pluronic-based metronidazole in situ gelling formu- lations for vaginal application. Acta pharmaceutica, 62(1), 59-70. doi: 10.2478/v10007-012-0009-y.
  • ICH. (2005). ICH Topic Q2 (R1) Validation of Analytical Procedures: Text and Methodology. International Conference on Harmoniza- tion 1994 (p.17).
  • Isacchi, B., Bergonzi, M. C., Grazioso, M., Righeschi, C., Pietretti, A., Severini, C., & Bilia, A. R. (2012). Artemisinin and artemisinin plus curcumin liposomal formulations: enhanced antimalarial efficacy against Plasmodium berghei-infected mice. European Journal of Pharmaceutics and Biopharmaceutics, 80(3), 528-534. doi: 10.1016/j.ejpb.2011.11.015.
  • Jain, A., Doppalapudi, S., Domb, A. J., & Khan, W. (2016). Tacroli- mus and curcumin co-loaded liposphere gel: Synergistic com- bination towards management of psoriasis. Journal of Controlled Release, 243, 132-145. doi: 10.1016/j.jconrel.2016.10.004.
  • Jangle, R. D., & Thorat, B. N. (2013). Reversed-phase high- performance liquid chromatography method for analysis of curcuminoids and curcuminoid-loaded liposome formula- tion. Indian Journal of Pharmaceutical Sciences, 75(1), 60-66. doi: 10.4103/0250-474X.113555.
  • Jayaprakasha, G. K., Jagan Mohan Rao, L., & Sakariah, K. K. (2002). Improved HPLC method for the determination of curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Journal of Agricultural and Food Chemistry, 50(13), 3668-3672. doi: 10.1021/ jf025506a.
  • Ji, L., Jiang, Y., Wen, J., Fan, G., Wu, Y., & Zhang, C. (2009). A rapid and simple HPLC method for the determination of curcumin in rat plasma: assay development, validation and application to a pharmacokinetic study of curcumin liposome. Biomedical Chro- matography, 23(11), 1201-1207. doi: 10.1002/bmc.1244.
  • Lakshmi, Y. S., Kumar, P., Kishore, G., Bhaskar, C., & Kondapi, A. K. (2016). Triple combination MPT vaginal microbicide using cur- cumin and efavirenz loaded lactoferrin nanoparticles. Scientific reports, 6(1), 1-13. doi: 10.1038/srep25479.
  • Mun, S. H., Joung, D. K., Kim, Y. S., Kang, O. H., Kim, S. B., Seo, Y. S., ... & Kwon, D. Y. (2013). Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus. Phytomedi- cine, 20(8-9), 714-718. doi: 10.1016/J.PHYMED.2013.02.006.
  • Rangel-Castañeda, I. A., Hernández-Hernández, J. M., Pérez-Ran- gel, A., González-Pozos, S., Carranza-Rosales, P., Charles-Niño, C. L., ... & Castillo-Romero, A. (2018). Amoebicidal activity of curcumin on Entamoeba histolytica trophozoites. Journal of Pharmacy and Pharmacology, 70(3), 426-433. doi: 10.1111/jphp.12867.
  • Sasidharan, N. K., Sreekala, S. R., Jacob, J., & Nambisan, B. (2014). In vitro synergistic effect of curcumin in combination with third generation cephalosporins against bacteria associated with infectious diarrhea. BioMed Research International, 2014. doi: 10.1155/2014/561456.
  • Singh, S., & Giri, S. (2013). Curcumin protects oxidative stress and DNA damage induced by metronidazole and gamma radiation in vivo. Paper presented at the: Environmental Mutagen Society of India and national conference on current perspectives on en- vironmental mutagenesis and human health, Mumbai (India), Abstract retrieved from https://www.osti.gov/etdeweb/bib- lio/22082419
  • Teow, S. Y., & Ali, S. A. (2015). Synergistic antibacterial activity of Curcumin with antibiotics against Staphylococcus aureus. Paki- stan Journal of Pharmaceutical Sciences, 28(6), 2109-2114.
  • Topal, M., Şenel, G. U., Arslan Topal, E. I., & Öbek, E. (2015). Antibiyo-tikler ve kullanım alanları. Erciyes Üniversitesi Fen Bilimleri Enstitüsü Fen Bilimleri Dergisi, 31(3), 121-127.
  • USP, (2015). U.S. Pharmacopoeia-national formulary [USP 38 NF 33]. Rockville, Md United States Pharmacopeial Convention. volume 1.
  • Venkateshwaran, T. G., & Stewart, J. T. (1995). Determination of metronidazole in vaginal tissue by high-performance liquid chro- matography using solid-phase extraction. Journal of Chromatog- raphy B: Biomedical Sciences and Applications, 672(2), 300-304. doi: 10.1016/0378-4347(95)00217-7.
  • Wachter, B., Syrowatka, M., Obwaller, A., & Walochnik, J. (2014). In vitro efficacy of curcumin on Trichomonas vaginalis. Wiener klinische Wochenschrift, 126(1), 32-36. doi: 10.1007/s00508-014- 0522-8.
  • Yu, T., Malcolm, K., Woolfson, D., Jones, D. S., & Andrews, G. P. (2011). Vaginal gel drug delivery systems: understanding rheo- logical characteristics and performance. Expert Opinion on Drug Delivery, 8(10), 1309-1322. doi: 10.1517/17425247.2011.600119.
  • Yuan, Y., Cui, Y., Zhang, L., Zhu, H. P., Guo, Y. S., Zhong, B., ... & Chen, L. (2012). Thermosensitive and mucoadhesive in situ gel based on poloxamer as new carrier for rectal administration of nimesu- lide. International Journal of Pharmaceutics, 430(1-2), 114-119. doi: 10.1016/j.ijpharm.2012.03.054.
There are 33 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Original Article
Authors

Leyla Beba Pojarani 0000-0001-5051-4489

E. Vildan Burgaz 0000-0003-3245-5934

Esra Baloglu This is me 0000-0001-7285-6105

Project Number N/A
Publication Date December 30, 2022
Submission Date October 7, 2021
Published in Issue Year 2022 Volume: 52 Issue: 3

Cite

APA Beba Pojarani, L., Burgaz, E. V., & Baloglu, E. (2022). Development and validation of an RP-HPLC method for simultaneous determination of curcumin and metronidazole in combined dosage form. İstanbul Journal of Pharmacy, 52(3), 250-257. https://doi.org/10.26650/IstanbulJPharm.2022.1005453
AMA Beba Pojarani L, Burgaz EV, Baloglu E. Development and validation of an RP-HPLC method for simultaneous determination of curcumin and metronidazole in combined dosage form. iujp. December 2022;52(3):250-257. doi:10.26650/IstanbulJPharm.2022.1005453
Chicago Beba Pojarani, Leyla, E. Vildan Burgaz, and Esra Baloglu. “Development and Validation of an RP-HPLC Method for Simultaneous Determination of Curcumin and Metronidazole in Combined Dosage Form”. İstanbul Journal of Pharmacy 52, no. 3 (December 2022): 250-57. https://doi.org/10.26650/IstanbulJPharm.2022.1005453.
EndNote Beba Pojarani L, Burgaz EV, Baloglu E (December 1, 2022) Development and validation of an RP-HPLC method for simultaneous determination of curcumin and metronidazole in combined dosage form. İstanbul Journal of Pharmacy 52 3 250–257.
IEEE L. Beba Pojarani, E. V. Burgaz, and E. Baloglu, “Development and validation of an RP-HPLC method for simultaneous determination of curcumin and metronidazole in combined dosage form”, iujp, vol. 52, no. 3, pp. 250–257, 2022, doi: 10.26650/IstanbulJPharm.2022.1005453.
ISNAD Beba Pojarani, Leyla et al. “Development and Validation of an RP-HPLC Method for Simultaneous Determination of Curcumin and Metronidazole in Combined Dosage Form”. İstanbul Journal of Pharmacy 52/3 (December 2022), 250-257. https://doi.org/10.26650/IstanbulJPharm.2022.1005453.
JAMA Beba Pojarani L, Burgaz EV, Baloglu E. Development and validation of an RP-HPLC method for simultaneous determination of curcumin and metronidazole in combined dosage form. iujp. 2022;52:250–257.
MLA Beba Pojarani, Leyla et al. “Development and Validation of an RP-HPLC Method for Simultaneous Determination of Curcumin and Metronidazole in Combined Dosage Form”. İstanbul Journal of Pharmacy, vol. 52, no. 3, 2022, pp. 250-7, doi:10.26650/IstanbulJPharm.2022.1005453.
Vancouver Beba Pojarani L, Burgaz EV, Baloglu E. Development and validation of an RP-HPLC method for simultaneous determination of curcumin and metronidazole in combined dosage form. iujp. 2022;52(3):250-7.
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