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

Development and Validation of 1H Nuclear Magnetic Resonance Quantitative Method for Efavirenz API Quality Control

Author(s): Eduardo Gomes Rodrigues de Sousa*, Karina Rocha de Souza, Rosane Aguiar da Silva San Gil*, Thiago Frances Guimaraes, Renata Ribeiro de Castro, Leonardo Lucchetti and Erika Martins de Carvalho

Volume 20, Issue 9, 2024

Published on: 15 May, 2024

Page: [674 - 685] Pages: 12

DOI: 10.2174/0115734110307860240503080554

Price: $65

Abstract

Background: The pharmaceutical industry is constantly looking for a better way to ensure and improve its products' safety, quality, and effectiveness. Since there are many attributes of the drug substance and excipients that could potentially affect the Critical Quality Attributes (CQAs) of the intermediates and the final product, the evaluation of the raw material's physicochemical characteristics is crucial as they directly affect the quality, safety, efficacy, and lot-to-lot consistency. Scientists rely on methods, like HPLC, HPTLC, LC-MS, GC-MS, and NMR, to analyze these substances. The advantage of NMR is that it is considered a primary analytical method compared to other analytical techniques.

Objective: This work aimed to present a simple, rapid, specific, and accurate method by proton Nuclear Magnetic Resonance spectroscopy (1H-NMR) developed to determine the activity of the antiretroviral Efavirenz’s (EFZ) Active Pharmaceutical Ingredient (API). The method was based on quantitative NMR spectroscopy (qNMR).

Methods: A Bruker Avance spectrometer (11.7 Tesla, 500 MHz for 1H) with a 5mm probe was used. The 1H-NMR signal at 7.54 ppm corresponding to the analyte of interest was employed to quantify the drug. The method was validated for specificity, selectivity, intermediate precision, linearity, range of work, accuracy, and robustness.

Results: The method developed was specific and linear (r2 = 0.9998) with a value between 4.30 mg/mL and 12.40 mg/mL. The relative standard deviation for accuracy and precision was 0.4% or less. The method's robustness was demonstrated by changing four different parameters, and the difference among each was 1.2% or less. The results of this work have been found to be in agreement with those obtained from High-performance Liquid Chromatography (HPLC) analysis.

Conclusion: The proposed method has been found to be a valuable and practical tool for quality control. Its applicability to determining many APIs and saving solvent use and time is highlighted.

« Previous Next »
Graphical Abstract

[1]
Calixto, J.B. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents). Braz. J. Med. Biol. Res., 2000, 33(2), 179-189.
[http://dx.doi.org/10.1590/S0100-879X2000000200004] [PMID: 10657057]
[2]
Singh, J. International conference on harmonization of technical requirements for registration of pharmaceuticals for human use. J. Pharmacol. Pharmacother., 2015, 6(3), 185-187.
[http://dx.doi.org/10.4103/0976-500X.162004] [PMID: 26312010]
[3]
Yu, L.X. Pharmaceutical quality by design: product and process development, understanding, and control. Pharm. Res., 2008, 25(4), 781-791.
[http://dx.doi.org/10.1007/s11095-007-9511-1] [PMID: 18185986]
[4]
Yu, L.X.; Amidon, G.; Khan, M.A.; Hoag, S.W.; Polli, J.; Raju, G.K.; Woodcock, J. Understanding pharmaceutical quality by design. AAPS J., 2014, 16(4), 771-783.
[http://dx.doi.org/10.1208/s12248-014-9598-3] [PMID: 24854893]
[5]
Ali, J.; Pramod, K.; Tahir, M.A.; Charoo, N.A.; Ansari, S.H. Pharmaceutical product development: A quality by design approach. Int. J. Pharm. Investig., 2016, 6(3), 129-138.
[http://dx.doi.org/10.4103/2230-973X.187350] [PMID: 27606256]
[6]
Haleem, R.M.; Salem, M.Y.; Fatahallah, F.A.; Abdelfattah, L.E. Quality in the pharmaceutical industry – A literature review. Saudi Pharm. J., 2015, 23(5), 463-469.
[http://dx.doi.org/10.1016/j.jsps.2013.11.004] [PMID: 26594110]
[7]
Ross, J.E. Total quality management: Text, cases, and readings, 3rd ed; Routledge, 2017.
[http://dx.doi.org/10.1201/9780203735466]
[8]
FDA. Pharmaceutical quality for the 21st century a risk-based approach progress report. 2007. Available from: https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/pharmaceutical-quality-21st-century-risk-based-approach-progress-report
[9]
ICH. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, Pharmaceutical Development Q8(R2), 2009. 2009 Available from: https://database.ich.org/sites/default/files/Q8_R2_Guideline.pdf
[10]
Holm, P. Q8 (R2) Pharmaceutical Development. ICH quality guidelines: an implementation guide, 2017., 2017. Available from: https://database.ich.org/sites/default/files/Q8_R2_Guideline.pdf
[11]
Mishra, V.; Thakur, S.; Patil, A.; Shukla, A. Quality by design (QbD) approaches in current pharmaceutical set-up. Expert Opin. Drug Deliv., 2018, 15(8), 737-758.
[http://dx.doi.org/10.1080/17425247.2018.1504768] [PMID: 30044646]
[12]
Jagan, B. Quality by Design (QbD): Principles, underlying concepts, and regulatory prospects. Thaiphesatchasan, 2021, 45(1), 54-69.
[13]
Fukuda, I.M. Design of experiments (DoE) applied to pharmaceutical and analytical quality by design (QbD). Braz. J. Pharm. Sci., 2018, 54, e01006.
[14]
Taha, M.S.; Padmakumar, S.; Singh, A.; Amiji, M.M. Critical quality attributes in the development of therapeutic nanomedicines toward clinical translation. Drug Deliv. Transl. Res., 2020, 10(3), 766-790.
[http://dx.doi.org/10.1007/s13346-020-00744-1] [PMID: 32170656]
[15]
Namjoshi, S.; Dabbaghi, M.; Roberts, M.S.; Grice, J.E.; Mohammed, Y. Quality by design: Development of the quality target product profile (QTPP) for semisolid topical products. Pharmaceutics, 2020, 12(3), 287.
[http://dx.doi.org/10.3390/pharmaceutics12030287] [PMID: 32210126]
[16]
Bhoop, B.S. Quality by Design (QbD) for holistic pharma excellence and regulatory compliance. Pharm. Times, 2014, 8(46), 31-33.
[http://dx.doi.org/10.22159/ijap.2022v14i5.45300]
[17]
Medeiros, M.; Breitkreitz, M.C. Quality by design in pharmaceutical product and process development. In: Introduction to Quality by Design in Pharmaceutical Manufacturing and Analytical Development; Springer, 2023; pp. 91-116.
[http://dx.doi.org/10.1007/978-3-031-31505-3_5]
[18]
Jahani, M.; Fazly Bazzaz, B.S.; Akaberi, M.; Rajabi, O.; Hadizadeh, F. Recent progresses in analytical perspectives of degradation studies and impurity profiling in pharmaceutical developments: An updated review. Crit. Rev. Anal. Chem., 2023, 53(5), 1094-1115.
[http://dx.doi.org/10.1080/10408347.2021.2008226] [PMID: 35108132]
[19]
Parmar, I.; Rathod, H.; Shaik, S. A review: Recent trends in analytical techniques for characterization and structure elucidation of impurities in the drug substances. Indian J. Pharm. Sci., 2021, 83(3), 402-415.
[http://dx.doi.org/10.36468/pharmaceutical-sciences.789]
[20]
Patel, K.; Patel, J.; Patel, M.; Rajput, G.; Patel, H. Introduction to hyphenated techniques and their applications in pharmacy. Pharm. Methods, 2010, 1(1), 2-13.
[http://dx.doi.org/10.4103/2229-4708.72222] [PMID: 23781411]
[21]
Tulshiram, D.G.; Umamaheshwari, D. Novel analytical techniques used in identification and isolation of impurities in pharmaceuticals an overview. J. Pharm. Sci. & Res., 2020, 12(1), 37-42.
[22]
Maggio, R.M.; Calvo, N.L.; Vignaduzzo, S.E.; Kaufman, T.S. Pharmaceutical impurities and degradation products: Uses and applications of NMR techniques. J. Pharm. Biomed. Anal., 2014, 101, 102-122.
[http://dx.doi.org/10.1016/j.jpba.2014.04.016] [PMID: 24853620]
[23]
Geven, A.; Özcan, S.; Levent, S.; Can, N.Ö. Development of a new, fully validated LC-MS/MS method for the analysis of flibanserin in pharmaceutical preparations and comparison of the chromatographic performance with six stationary phase types. Curr. Anal. Chem., 2023, 19(7), 541-549.
[http://dx.doi.org/10.2174/1573411019666230726121218]
[24]
Hai, C.T.; Uyen, N.T.; Giang, D.H.; Minh, N.T.T.; Duong, H.T.; Nhat Le, B.T.; Thanh, N.T.; Minh, T.N.; Dat, N.T. Quantitative HPLC-based metabolomics approach for the discrimination of processed rhizomes of atractylodes macrocephala. Curr. Anal. Chem., 2024, 20(1), 41-51.
[http://dx.doi.org/10.2174/0115734110283469231204061131]
[25]
Nalakath, J. Method development and validation for simultaneous detection of corticosteroids, small peptides, SARMs and quaternary ammonium drugs in camel urine for doping control applications. Curr. Anal. Chem., 2024, 20(1), 14-28.
[http://dx.doi.org/10.2174/0115734110276595231222050709]
[26]
Malz, F.; Jancke, H. Validation of quantitative NMR. J. Pharm. Biomed. Anal., 2005, 38(5), 813-823.
[http://dx.doi.org/10.1016/j.jpba.2005.01.043] [PMID: 15893442]
[27]
Pauli, G.F.; Gödecke, T.; Jaki, B.U.; Lankin, D.C. Quantitative 1H NMR. Development and potential of an analytical method: An update. J. Nat. Prod., 2012, 75(4), 834-851.
[http://dx.doi.org/10.1021/np200993k] [PMID: 22482996]
[28]
Holzgrabe, U. Quantitative NMR spectroscopy in pharmaceutical applications. Prog. Nucl. Magn. Reson. Spectrosc., 2010, 57(2), 229-240.
[http://dx.doi.org/10.1016/j.pnmrs.2010.05.001] [PMID: 20633364]
[29]
Holzgrabe, U.; Wawer, I.; Diehl, B. NMR spectroscopy in drug development and analysis; John Wiley & Sons, 2008.
[30]
Santos, M.S.; Colnago, L.A. Validation of quantitative 1H NMR method for the analysis of pharmaceutical formulations. Quim. Nova, 2013, 36, 324-330.
[http://dx.doi.org/10.1590/S0100-40422013000200020]
[31]
Eltemur, D.; Robatscher, P.; Oberhuber, M.; Scampicchio, M.; Ceccon, A. Applications of solution NMR spectroscopy in quality assessment and authentication of bovine milk. Foods, 2023, 12(17), 3240.
[http://dx.doi.org/10.3390/foods12173240] [PMID: 37685173]
[32]
Xie, Y.; Zheng, D.; Yang, T.; Zhang, Z.; Xu, W.; Liu, H.; Li, W. Head-to-head comparison of high-performance liquid chromatography versus nuclear magnetic resonance for the quantitative analysis of carbohydrates in yiqi fumai lyophilized injection. Molecules, 2023, 28(2), 765.
[http://dx.doi.org/10.3390/molecules28020765] [PMID: 36677822]
[33]
Huang, T.; Zhang, W.; Dai, X.; Li, N.; Huang, L.; Quan, C.; Li, H.; Yang, Y. High performance liquid chromatography-quantitative nuclear magnetic resonance (HPLC-qNMR) with a two-signal suppression method for purity assessment of avermectin B1a. Anal. Methods, 2016, 8(22), 4482-4486.
[http://dx.doi.org/10.1039/C6AY00570E]
[34]
Crook, A.A.; Powers, R. Quantitative NMR-based biomedical metabolomics: Current status and applications. Molecules, 2020, 25(21), 5128.
[http://dx.doi.org/10.3390/molecules25215128] [PMID: 33158172]
[35]
Giraudeau, P. Challenges and perspectives in quantitative NMR. Magn. Reson. Chem., 2017, 55(1), 61-69.
[http://dx.doi.org/10.1002/mrc.4475] [PMID: 27370178]
[36]
Khalil, A.; Kashif, M. Nuclear magnetic resonance spectroscopy for quantitative analysis: A review for its application in the chemical, pharmaceutical and medicinal domains. Crit. Rev. Anal. Chem., 2023, 53(5), 997-1011.
[http://dx.doi.org/10.1080/10408347.2021.2000359] [PMID: 34752175]
[37]
Chen, X.; Guo, Y.; Hu, Y.; Yu, B.; Qi, J. Quantitative analysis of highly similar salvianolic acids with 1 H qNMR for quality control of traditional Chinese medicinal preparation Salvianolate Lyophilized Injection. J. Pharm. Biomed. Anal., 2016, 124, 281-287.
[http://dx.doi.org/10.1016/j.jpba.2016.02.016] [PMID: 26970983]
[38]
Wang, T.; Liu, Q.; Wang, M.; Zhou, J.; Yang, M. Quantitative 1H NMR methodology for purity assay with high accuracy. Accredit. Qual. Assur., 2023, 28(6), 253-260.
[http://dx.doi.org/10.1007/s00769-023-01550-1]
[39]
Silva, R.C.A.; de Sousa, E.G.R.; Mazzei, J.L.; de Carvalho, E.M. Quantitative 1H NMR method for analyzing primaquine diphosphate in active pharmaceutical ingredients. J. Pharm. Biomed. Anal., 2022, 210, 114585.
[http://dx.doi.org/10.1016/j.jpba.2022.114585] [PMID: 35042143]
[40]
Pan, J.Y.; Zhao, F.; Li, W.Z.; Qu, H.B. Quantitative NMR spectroscopy and its application in quality control of Chinese medicinal injection. Chin. J. Chin. Mater. Med., 2022, 47(3), 569-574.
[http://dx.doi.org/10.19540/j.cnki.cjcmm.20210906.302] [PMID: 35178937]
[41]
Giancaspro, G.; Adams, K.M.; Bhavaraju, S.; Corbett, C.; Diehl, B.; Freudenberger, J.C.; Fritsch, K.; Krishnamurthy, K.; Laatikainen, P.; Martos, G.; Miura, T.; Nam, J.W.; Niemitz, M.; Nishizaki, Y.; Sugimoto, N.; Obkircher, M.; Phansalkar, R.; Ray, G.J.; Saito, T.; Sørensen, D.; Urbas, A.; Napolitano, J.G.; Tadjimukhamedov, F.; Bzhelyansky, A.; Liu, Y.; Pauli, G.F. The qNMR summit 5.0: Proceedings and status of qNMR technology. Anal. Chem., 2021, 93(36), 12162-12169.
[http://dx.doi.org/10.1021/acs.analchem.1c02056] [PMID: 34473490]
[42]
Efavirenz. In: Aronson, J.K., Ed.; Meyler’s Side Effects of Drugs, 16th ed; Elsevier: Oxford, 2016, pp. 25-31.
[http://dx.doi.org/10.1016/B978-0-444-53717-1.00675-2]
[43]
Fortin, C.; Joly, V. Efavirenz for HIV-1 infection in adults: An overview. Expert Rev. Anti Infect. Ther., 2004, 2(5), 671-684.
[http://dx.doi.org/10.1586/14789072.2.5.671] [PMID: 15482231]
[44]
Marzolini, C.; Telenti, A.; Decosterd, L.A.; Greub, G.; Biollaz, J.; Buclin, T. Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. AIDS, 2001, 15(1), 71-75.
[http://dx.doi.org/10.1097/00002030-200101050-00011] [PMID: 11192870]
[45]
Shubber, Z.; Calmy, A.; Meyer, A.I.; Vitoria, M.; Théry, R.F.; Shaffer, N.; Hargreaves, S.; Mills, E.J.; Ford, N. Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy. AIDS, 2013, 27(9), 1403-1412.
[http://dx.doi.org/10.1097/QAD.0b013e32835f1db0] [PMID: 23343913]
[46]
Tovar-y-Romo, L.B.; Bumpus, N.N.; Pomerantz, D.; Avery, L.B.; Sacktor, N.; McArthur, J.C.; Haughey, N.J. Dendritic spine injury induced by the 8-hydroxy metabolite of efavirenz. J. Pharmacol. Exp. Ther., 2012, 343(3), 696-703.
[http://dx.doi.org/10.1124/jpet.112.195701] [PMID: 22984227]
[47]
Andriguetti, N.B.; Barratt, D.T.; Tucci, J.; Pumuye, P.; Somogyi, A.A. Instability of efavirenz metabolites identified during method development and validation. J. Pharm. Sci., 2021, 110(10), 3362-3366.
[http://dx.doi.org/10.1016/j.xphs.2021.06.028] [PMID: 34175301]
[48]
National List of Essential Medicines; Ministry of Health: Brazil, 2022.
[49]
Shamsipur, M. Fluorine-19 nuclear magnetic resonance (19F NMR) as a powerful technique for the assay of anti-HIV drug efavirenz in human serum and pharmaceutical formulations. Afr. J. Pharm. Pharmacol., 2011, 5(13), 1573-1579.
[http://dx.doi.org/10.5897/AJPP11.275]
[50]
Sousa, E.G.R.; Carvalho, E.M.; San Gil, R.A.S.; Santos, T.C.; Borré, L.B.; Santos-Filho, O.A.; Ellena, J. Solution and solid state nuclear magnetic resonance spectroscopic characterization of efavirenz. J. Pharm. Sci., 2016, 105(9), 2656-2664.
[http://dx.doi.org/10.1016/j.xphs.2015.10.006] [PMID: 26886313]
[51]
Braga, S.S.; El-Saleh, F.; Lysenko, K.; Paz, F.A.A. Inclusion compound of efavirenz and γ-cyclodextrin: Solid state studies and effect on solubility. Molecules, 2021, 26(3), 519.
[http://dx.doi.org/10.3390/molecules26030519] [PMID: 33498239]
[52]
Endres, S.; Karaev, E.; Hanio, S.; Schlauersbach, J.; Kraft, C.; Rasmussen, T.; Luxenhofer, R.; Böttcher, B.; Meinel, L.; Pöppler, A.C. Concentration and composition dependent aggregation of Pluronic- and Poly-(2-oxazolin)-Efavirenz formulations in biorelevant media. J. Colloid Interface Sci., 2022, 606(Pt 2), 1179-1192.
[http://dx.doi.org/10.1016/j.jcis.2021.08.040] [PMID: 34487937]
[53]
Mazurek, A.H.; Szeleszczuk, Ł. A review of applications of solid-state nuclear magnetic resonance (ssNMR) for the analysis of cyclodextrin-including systems. Int. J. Mol. Sci., 2023, 24(4), 3648.
[http://dx.doi.org/10.3390/ijms24043648] [PMID: 36835054]
[54]
ANVISA. Brazilian Pharmacopoeia: Efavirenz; ANVISA: Brazil, 2010.
[55]
Farrant, R.D.; Lindon, J.C. NMR parameter survey, 13C. Encyclopedia of Spectroscopy and Spectrometry, 3rd ed;; Lindon, J.C.; Tranter, G.E.; Koppenaal, D.W. Eds.; Academic Press: Oxford, 2017, pp. 181-186.
[http://dx.doi.org/10.1016/B978-0-12-803224-4.00112-6]
[56]
Ernst, R.R.; Anderson, W.A. Application of fourier transform spectroscopy to magnetic resonance. Rev. Sci. Instrum., 1966, 37(1), 93-102.
[http://dx.doi.org/10.1063/1.1719961]
[57]
Wei, R.; Dickson, C.L.; Uhrín, D.; Lloyd-Jones, G.C. Rapid estimation of T1 for quantitative NMR. J. Org. Chem., 2021, 86(13), 9023-9029.
[http://dx.doi.org/10.1021/acs.joc.1c01007] [PMID: 34155887]
[58]
Zhang, Y.Y.; Zhang, J.; Zhang, W.X.; Wang, Y.; Wang, Y.H.; Yang, Q.Y.; Wu, S. Quantitative 1H nuclear magnetic resonance method for assessing the purity of dipotassium glycyrrhizinate. Molecules, 2021, 26(12), 3549.
[http://dx.doi.org/10.3390/molecules26123549] [PMID: 34200734]
[59]
Yin, T.; Lu, J.; Liu, Q.; Zhu, G.; Zhang, W.; Jiang, Z. Validated quantitative 1H NMR method for simultaneous quantification of indole alkaloids in Uncaria rhynchophylla. ACS Omega, 2021, 6(47), 31810-31817.
[http://dx.doi.org/10.1021/acsomega.1c04464] [PMID: 34870003]
[60]
Rizzo, V.; Pinciroli, V. Quantitative NMR in synthetic and combinatorial chemistry. J. Pharm. Biomed. Anal., 2005, 38(5), 851-857.
[http://dx.doi.org/10.1016/j.jpba.2005.01.045] [PMID: 16087047]
[61]
Bharti, S.K.; Roy, R. Quantitative 1H NMR spectroscopy. Trends Analyt. Chem., 2012, 35, 5-26.
[http://dx.doi.org/10.1016/j.trac.2012.02.007]
[62]
Pauli, G.F.; Jaki, B.U.; Lankin, D.C. A routine experimental protocol for qHNMR illustrated with Taxol. J. Nat. Prod., 2007, 70(4), 589-595.
[http://dx.doi.org/10.1021/np060535r] [PMID: 17298095]
[63]
Bahadoor, A.; Brinkmann, A.; Melanson, J.E. 13C-satellite decoupling strategies for improving accuracy in quantitative nuclear magnetic resonance. Anal. Chem., 2021, 93(2), 851-858.
[http://dx.doi.org/10.1021/acs.analchem.0c03428] [PMID: 33300782]
[64]
Pauli, G.F.; Chen, S.N.; Simmler, C.; Lankin, D.C.; Gödecke, T.; Jaki, B.U.; Friesen, J.B.; McAlpine, J.B.; Napolitano, J.G. Importance of purity evaluation and the potential of quantitative 1H NMR as a purity assay. J. Med. Chem., 2014, 57(22), 9220-9231.
[http://dx.doi.org/10.1021/jm500734a] [PMID: 25295852]
[65]
Singh, N.; Taibon, J.; Pongratz, S.; Geletneky, C. Quantitative NMR (qNMR) spectroscopy based investigation of the absolute content, stability and isomerization of 25-hydroxyvitamin D2/D3 and 24(R),25-dihydroxyvitamin D2 in solution phase. Sci. Rep., 2022, 12(1), 3014.
[http://dx.doi.org/10.1038/s41598-022-06948-4] [PMID: 35194108]
[66]
Holzgrabe, U.; Deubner, R.; Schollmayer, C.; Waibel, B. Quantitative NMR spectroscopy—Applications in drug analysis. J. Pharm. Biomed. Anal., 2005, 38(5), 806-812.
[http://dx.doi.org/10.1016/j.jpba.2005.01.050] [PMID: 15893899]
[67]
Schoenberger, T. Guideline for qNMR analysis; European Network of Forensic Science Institutes: Wiesbaden, Germany, 2019.
[68]
Liang, X.; Du, L.; Su, F.; Parekh, H.S.; Su, W. The application of quantitative NMR for the facile, rapid and reliable determination of clindamycin phosphate in a conventional tablet formulation. Magn. Reson. Chem., 2014, 52(4), 178-182.
[http://dx.doi.org/10.1002/mrc.4048] [PMID: 24464591]
[69]
ANVISA Analytical and bioanalytical method validation guide – Resolution no. 899; ANVISA: Brazil, 2003.
[70]
Bastos, M.M.; Costa, C.C.P.; Bezerra, T.C.; da Silva, F.C.; Boechat, N. Efavirenz a nonnucleoside reverse transcriptase inhibitor of first-generation: Approaches based on its medicinal chemistry. Eur. J. Med. Chem., 2016, 108, 455-465.
[http://dx.doi.org/10.1016/j.ejmech.2015.11.025] [PMID: 26708112]
[71]
de Ribeiro, A.J.A.; de Campos, L.M.M.; Alves, R.J.; Lages, G.P.; Pianetti, G.A. Efavirenz related compounds preparation by hydrolysis procedure: Setting reference standards for chromatographic purity analysis. J. Pharm. Biomed. Anal., 2007, 43(1), 298-303.
[http://dx.doi.org/10.1016/j.jpba.2006.06.010] [PMID: 16854550]
[72]
CH. Validation of analytical procedures: Text and methodology Q2 (R1). 2005. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-q2r1-validation-analytical-procedures-text-and-methodology-step-5-first-version_en.pdf
[73]
ANVISA. Agência Nacional de Vigilância Sanitária. Resolução da diretoria colegiada- RDC Nº 166, de 24 de julho de, 2017. https://antigo.anvisa.gov.br/documents/10181/2721567/RDC_166_2017_COMP.pdf/d5fb92b3-6c6b-4130-8670-4e3263763401
[74]
Qin, L.; Wang, X.; Lu, D. Quantitative determination and validation of topiramate and its tablet formulation by 1H-NMR spectroscopy. Anal. Methods, 2019, 11(5), 661-668.
[http://dx.doi.org/10.1039/C8AY02316F]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy