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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Development and Validation of a Simple HPLC-UV Method to Assay DEET Repellents and its Application to Different Commercial Forms

Author(s): Juliana dos Santos, Rebeca Lino Lourenço, Priscila Rosa and Andréa Inês Horn Adams*

Volume 17, Issue 8, 2021

Published on: 03 July, 2020

Page: [1051 - 1059] Pages: 9

DOI: 10.2174/1573412916999200703133456

Price: $65

Abstract

Background: N’,N’-diethyl-m-toluamide (DEET) is the most widely used repellent substance worldwide. It is formulated as aerosol, solution, lotion, gel and patches. However, the official compendia report monographs to analyze only DEET drug substance and solution.

Objective: In this study, an isocratic HPLC method was validated to assay DEET in lotion, gel and solution, under the same analytical conditions.

Methods: The method was validated according to ICH requirements and DEET detection was achieved at around 11 min, using a C-18 column, a mobile phase composed by methanol, acetonitrile and water pH 4.5 (45:10:45), flow rate at 1 mL min-1 and detection at 270 nm.

Results: A linear relationship was observed in the range of 2.5 to 100 μg mL-1, the method was precise (relative standard deviation < 2%) and accuracy was demonstrated by DEET recovery values ranging from 99.5 to 100.2%. The specificity was studied by a forced degradation test, where degradation products were observed after alkaline degradation and ultraviolet radiation. Appropriate resolution between DEET, degradation products and excipient peaks indicated the method specificity. Robustness was evaluated by a full factorial design, and no effect on DEET assay was observed under simultaneous variation in analytical parameters. The method was applied to assay nine marketed formulations, demonstrating its good applicability.

Conclusion: The validated HPLC method was successfully applied to the quantitative analysis of DEET in lotion, gel and solution, contributing to improve the quality control and the efficacy of these formulations.

Keywords: DEET, repellents, HPLC-UV, lotion, gel, solution.

Graphical Abstract
[1]
Tavares, M.; da Silva, M.R.M.; de Oliveira de Siqueira, L.B.; Rodrigues, R.A.S.; Bodjolle-d’Almeida, L.; Dos Santos, E.P.; Ricci-Júnior, E. Trends in insect repellent formulations: A review. Int. J. Pharm., 2018, 539(1-2), 190-209.
[http://dx.doi.org/10.1016/j.ijpharm.2018.01.046] [PMID: 29410208]
[2]
Islam, J.; Zaman, K.; Duarah, S.; Raju, P.S.; Chattopadhyay, P. Mosquito repellents: An insight into the chronological perspectives and novel discoveries. Acta Trop., 2017, 167(2), 216-230.
[http://dx.doi.org/10.1016/j.actatropica.2016.12.031] [PMID: 28040483]
[3]
Brown, M.; Hebert, A.A. Insect repellents: an overview. J. Am. Acad. Dermatol., 1997, 36(2 Pt 1), 243-249.
[http://dx.doi.org/10.1016/S0190-9622(97)70289-5] [PMID: 9039177]
[4]
Roy, D.N.; Goswami, R.; Pal, A. The insect repellents: A silent environmental chemical toxicant to the health. Environ. Toxicol. Pharmacol., 2017, 50, 91-102.
[http://dx.doi.org/10.1016/j.etap.2017.01.019] [PMID: 28171823]
[5]
DeGennaro, M. The mysterious multi-modal repellency of DEET. Fly (Austin), 2015, 9(1), 45-51.
[http://dx.doi.org/10.1080/19336934.2015.1079360] [PMID: 26252744]
[6]
Debboun, M.; Frances, S.P.; Strickman, D. Insect repellents handbook; CRC Press: Boca Raton, FL, 2014, p. 409.http://www.crcnetbase.com/isbn/9781466553583
[http://dx.doi.org/10.1201/b17407]
[7]
Yoon, J.K.; Kim, K.C.; Cho, Y.; Gwon, Y.D.; Cho, H.S.; Heo, Y.; Park, K.; Lee, Y.W.; Kim, M.; Oh, Y.K.; Kim, Y.B. Comparison of repellency effect of mosquito repellents for deet, citronella, and fennel oil. J. Parasitol. Res., 2015, 2015361021.
[http://dx.doi.org/10.1155/2015/361021] [PMID: 26527362]
[8]
WHO. Guidelines for efficacy testing of mosquito repellents for human skin. 2009, 1-6.
[9]
Koren, G.; Matsui, D.; Bailey, B. DEET-based insect repellents: safety implications for children and pregnant and lactating women. CMAJ, 2003, 169(3), 209-212.
[PMID: 12900480]
[10]
Siddiqui, M.R.; AlOthman, A.A.; Rahman, N. Analytical techniques in pharmaceutical analysis: a review. AJC, 2017, 10, S1409-S1421.
[http://dx.doi.org/10.1016/j.arabjc.2013.04.016]
[11]
USP38. The United States Pharmacopoeia; United States Pharmacopeical Conventiom: Rockville, 2015.
[12]
Skoog, D.A.; Holler, F.J.; Nieman, T.A. Principle of Instrumental Analysis. 5; Mc Graw-Hill: Madrid, 2001.
[13]
USP39. The United States Pharmacopoeia; United States Pharmacopeical Conventiom: Rockville, 2016.
[14]
Sibaja, A.M.A.; Fandaruff, C.; Delgado, M.T.L.N. N -Diethyl- meta -toluamide (deet) in repellent solutions : development and validation of an analytical method. Rev. Bras. Farm., 2013, 94(3), 273-278.
[15]
Song, W.; Cooper, W.J.; Peake, B.M.; Mezyk, S.P.; Nickelsen, M.G.; O’Shea, K.E. Free-radical-induced oxidative and reductive degradation of N,N′-diethyl-m-toluamide (DEET): Kinetic studies and degradation pathway. Water Res., 2009, 43(3), 635-642.
[http://dx.doi.org/10.1016/j.watres.2008.11.018] [PMID: 19054538]
[16]
Kuklenyik, P.; Baker, S.E.; Bishop, A.M.; Morales-A, P.; Calafat, A.M. On-line solid phase extraction-high performance liquid chromatography-isotope dilution-tandem mass spectrometry approach to quantify N,N-diethyl-m-toluamide and oxidative metabolites in urine. Anal. Chim. Acta, 2013, 787, 267-273.
[http://dx.doi.org/10.1016/j.aca.2013.05.055] [PMID: 23830449]
[17]
Smallwood, A.W.; DeBord, K.E.; Lowry, L.K.N.N. N′-diethyl-m-toluamide (m-DET): analysis of an insect repellent in human urine and serum by high-performance liquid chromatography. J. Anal. Toxicol., 1992, 16(1), 10-13.
[http://dx.doi.org/10.1093/jat/16.1.10] [PMID: 1640692]
[18]
Abu-Qare, A.W.; Abou-Donia, M.B. Development of a high-performance liquid chromatographic method for the quantification of chlorpyrifos, pyridostigmine bromide, N,N-diethyl-m-toluamide and their metabolites in rat plasma and urine. J. Chromatogr. B Biomed. Sci. Appl., 2001, 754(2), 533-538.
[http://dx.doi.org/10.1016/S0378-4347(01)00028-7] [PMID: 11339298]
[19]
Kasichayanula, S.; House, J.D.; Wang, T.; Gu, X. Simultaneous analysis of insect repellent DEET, sunscreen oxybenzone and five relevant metabolites by reversed-phase HPLC with UV detection: application to an in vivo study in a piglet model. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2005, 822(1-2), 271-277.
[http://dx.doi.org/10.1016/j.jchromb.2005.06.015] [PMID: 15993660]
[20]
Yu, Z.; Sun, Y.; Zhang, G.; Zhang, C. Degradation of deet in aqueous solution by water falling film dielectric barrier discharge: effect of three operating modes and analysis of the mechanism and degradation pathway. Chem. Eng. J., 2017, 317, 90-102.
[http://dx.doi.org/10.1016/j.cej.2017.02.068]
[21]
Tay, K.S.; Rahman, N.A.; Abas, M.R.; Abas, B. Degradation of DEET by ozonation in aqueous solution. Chemosphere, 2009, 76(9), 1296-1302.
[http://dx.doi.org/10.1016/j.chemosphere.2009.06.007] [PMID: 19570564]
[22]
Ma, X.; Feng, F.; Yang, Y.; Dang, X.; Huang, J.; Chen, H. Magnetic solid-phase extraction of n,n-diethyl-m-toluamide from baby toilet water prior to its hplc-uv detection. J. Chromatogr. Sci., 2017, 55(6), 662-668.
[http://dx.doi.org/10.1093/chromsci/bmx015] [PMID: 28334987]
[23]
Zhang, H.; Watts, S.; Philix, M.C.; Snyder, S.A.; Ong, C.N. Occurrence and distribution of pesticides in precipitation as revealed by targeted screening through GC-MS/MS. Chemosphere, 2018, 211, 210-217.
[http://dx.doi.org/10.1016/j.chemosphere.2018.07.151] [PMID: 30075377]
[24]
Kapelewska, J.; Kotowska, U.; Wiśniewska, K. Determination of personal care products and hormones in leachate and groundwater from Polish MSW landfills by ultrasound-assisted emulsification microextraction and GC-MS. Environ. Sci. Pollut. Res. Int., 2016, 23(2), 1642-1652.
[http://dx.doi.org/10.1007/s11356-015-5359-9] [PMID: 26381788]
[25]
ICH Harmonised Tripartite Guideline Validation of Analytical Procedures: Text and Methodology Q2(R1),, 2005.
[26]
Blessy, M.; Patel, R.D.; Prajapati, P.N.; Agrawal, Y.K. Development of forced degradation and stability indicating studies of drugs-A review. J. Pharm. Anal., 2014, 4(3), 159-165.
[http://dx.doi.org/10.1016/j.jpha.2013.09.003] [PMID: 29403878]
[27]
Brasil. Agência Nacional de Vigilância Sanitária RDC N° 166, de 24 de Julho de 2017. Dispõe Sobre a Validação de Métodos Analíticos e Dá Outras Providências; Brasil, 2017.
[28]
ICH Harmonised Tripartite Guideline Stability Testing: Photostability Testing of New Drug Substances and Products Q1B, 1996.
[29]
Gawande, V.T.; Bothara, K.G.; Marathe, A.M. Stress studies and identification of degradation products of cephalexin using LC–PDA and LC–MS/MS. Chromatographia, 2017, 80(10), 1545-1552.
[http://dx.doi.org/10.1007/s10337-017-3385-0]
[30]
Shabir, G.A. Validation of high-performance liquid chromatography methods for pharmaceutical analysis. Understanding the differences and similarities between validation requirements of the US Food and Drug Administration, the US Pharmacopeia and the International Conference on Harmonization. J. Chromatogr. A, 2003, 987(1-2), 57-66.
[http://dx.doi.org/10.1016/S0021-9673(02)01536-4] [PMID: 12613797]
[31]
Ocaña-González, J.A.; Villar-Navarro, M.; Ramos-Payán, M.; Fernández-Torres, R.; Bello-López, M.A. New developments in the extraction and determination of parabens in cosmetics and environmental samples. A review. Anal. Chim. Acta, 2015, 858, 1-15.
[http://dx.doi.org/10.1016/j.aca.2014.07.002] [PMID: 25597796]
[32]
Alsante, K.M.; Ando, A.; Brown, R.; Ensing, J.; Hatajik, T.D.; Kong, W.; Tsuda, Y. The role of degradant profiling in active pharmaceutical ingredients and drug products. Adv. Drug Deliv. Rev., 2007, 59(1), 29-37.
[http://dx.doi.org/10.1016/j.addr.2006.10.006] [PMID: 17187892]
[33]
Brasil. Agência Nacional de Vigilância Sanitária. RDC N° 58, de 20 de dezembro de Estabelece parâmetros para a notificação, identificação e qualificação de produtos de degradação em medicamentos com substâncias ativas sintéticas e semissintéticas, classificados como novos, genéricos e similares, e dá outras providências; Brasil, 2013.

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