Abstract
Background: This study aimed to develop a sensitive, rapid method based on HPLC-MS/MS for the quantification of Montelukast in human plasma utilizing Montelukast-D6 as an internal standard. Montelukast is a leukotriene inhibitor and is used to prevent asthma attacks in adults and children.
Method: Separation was achieved using Thermo Hypersil GOLD™ Cyano HPLC columns (50 × 4.6 mm; 5 μm) with a mobile phase consisting of 0.5 mM ammonium chloride: ACN (20:80%; v/v).
Results: The method was found to be linear over a concentration range of 10.0 - 600.0 ng/mL with a correlation coefficient (r2) ≥ 0. 0.9989. The stabilities of Montelukast and internal standard were assessed in several conditions with recovery results > 85%. The precision results were less than 4.0%, while the accuracy results were within 93.0 107.0%. The method proved to be selective with no matrix effect.
Conclusion: This method was found to be highly reproducible and was utilized successfully for the analysis of plasma samples following the oral administration of Montelukast (10 mg) in 28 healthy male human volunteers.
Graphical Abstract
[1]
Aldea Perona, A.; García-Sáiz, M.; Sanz Álvarez, E. Psychiatric disorders and montelukast in children: A disproportionality analysis of the vigibase®. Drug Saf., 2016, 39(1), 69-78.
[http://dx.doi.org/10.1007/s40264-015-0360-2] [PMID: 26620206]
[http://dx.doi.org/10.1007/s40264-015-0360-2] [PMID: 26620206]
[2]
Allen-Ramey, F.C.; Bukstein, D.; Luskin, A.; Sajjan, S.G.; Markson, L.E. Administrative claims analysis of asthma-related health care utilization for patients who received inhaled corticosteroids with either montelukast or salmeterol as combination therapy. J. Manag. Care Pharm., 2006, 12(4), 310-321.
[http://dx.doi.org/10.18553/jmcp.2006.12.4.310] [PMID: 16792437]
[http://dx.doi.org/10.18553/jmcp.2006.12.4.310] [PMID: 16792437]
[3]
Bao, J.L.; Xinyuan-Gao; Han, Y.B.; Zhang, K.; Liu, L. Efficacy and safety of montelukast for pediatric obstructive sleep apnea syndrome. Medicine (Baltimore), 2021, 100(3), e23958.
[http://dx.doi.org/10.1097/MD.0000000000023958] [PMID: 33545976]
[http://dx.doi.org/10.1097/MD.0000000000023958] [PMID: 33545976]
[4]
Barnes, N.; Wei, L.X.; Reiss, T.F.; Leff, J.A.; Shingo, S.; Yu, C.; Edelman, J.M. Analysis of montelukast in mild persistent asthmatic patients with near-normal lung function. Respir. Med., 2001, 95(5), 379-386.
[http://dx.doi.org/10.1053/rmed.2001.1052] [PMID: 11392579]
[http://dx.doi.org/10.1053/rmed.2001.1052] [PMID: 11392579]
[5]
Bousquet, J.; Gaugris, S.; Kocevar, V.S.; Zhang, Q.; Yin, D.D.; Polos, P.G.; Bjermer, L. Increased risk of asthma attacks and emergency visits among asthma patients with allergic rhinitis: A subgroup analysis of the investigation of montelukast as a partner agent for complementary therapy. [corrected]. Clin. Exp. Allergy, 2005, 35(6), 723-727.
[http://dx.doi.org/10.1111/j.1365-2222.2005.02251.x] [PMID: 15969661]
[http://dx.doi.org/10.1111/j.1365-2222.2005.02251.x] [PMID: 15969661]
[6]
Carver, T. Exercise-induced asthma: Critical analysis of the protective role of montelukast. J. Asthma Allergy, 2009, 2, 93-103.
[http://dx.doi.org/10.2147/JAA.S7321] [PMID: 21437147]
[http://dx.doi.org/10.2147/JAA.S7321] [PMID: 21437147]
[7]
Castro-Rodriguez, J.A.; Rodrigo, G.J. The role of inhaled corticosteroids and montelukast in children with mild-moderate asthma: Results of a systematic review with meta-analysis. Arch. Dis. Child., 2010, 95(5), 365-370.
[http://dx.doi.org/10.1136/adc.2009.169177] [PMID: 19946008]
[http://dx.doi.org/10.1136/adc.2009.169177] [PMID: 19946008]
[8]
Hussein, H.R.; Gupta, A.; Broughton, S.; Ruiz, G.; Brathwaite, N.; Bossley, C.J. A meta-analysis of montelukast for recurrent wheeze in preschool children. Eur. J. Pediatr., 2017, 176(7), 963-969.
[http://dx.doi.org/10.1007/s00431-017-2936-6] [PMID: 28567533]
[http://dx.doi.org/10.1007/s00431-017-2936-6] [PMID: 28567533]
[9]
Ji, T.; Lu, T.; Qiu, Y.; Li, X.; Liu, Y.; Tai, J.; Guo, Y.; Zhang, J.; Wang, S.; Zhao, J.; Ni, X.; Xu, Z. The efficacy and safety of montelukast in children with obstructive sleep apnea: A systematic review and meta-analysis. Sleep Med., 2021, 78, 193-201.
[http://dx.doi.org/10.1016/j.sleep.2020.11.009] [PMID: 33465554]
[http://dx.doi.org/10.1016/j.sleep.2020.11.009] [PMID: 33465554]
[10]
Patil, S.; Pore, Y.V.; Kuchekar, B.S.; Mane, A.; Khire, V.G. Determination of montelukast sodium and bambuterol hydrochloride in tablets using RP HPLC. Indian J. Pharm. Sci., 2009, 71(1), 58-61.
[http://dx.doi.org/10.4103/0250-474X.51961] [PMID: 20177459]
[http://dx.doi.org/10.4103/0250-474X.51961] [PMID: 20177459]
[11]
Radhakrishna, T.; Narasaraju, A.; Ramakrishna, M.; Satyanarayana, A. Simultaneous determination of montelukast and loratadine by HPLC and derivative spectrophotometric methods. J. Pharm. Biomed. Anal., 2003, 31(2), 359-368.
[http://dx.doi.org/10.1016/S0731-7085(02)00650-7] [PMID: 12609675]
[http://dx.doi.org/10.1016/S0731-7085(02)00650-7] [PMID: 12609675]
[12]
Rana, N.S.; Rajesh, K.S.; Patel, N.N.; Patel, P.R.; Limbachiya, U.; Pasha, T.Y. Development and Validation of RP-HPLC Method for the Simultaneous Estimation of Montelukast Sodium and Ebastine in Tablet Dosage Form. Indian J. Pharm. Sci., 2013, 75(5), 599-602.
[PMID: 24403662]
[PMID: 24403662]
[13]
Ethiraj, T.; Revathi, R.; Thenmozhi, P.; Saravanan, V.S.; Ganesan, V. High performance liquid chromatographic method development for simultaneous analysis of doxofylline and montelukast sodium in a combined form. Pharm. Methods, 2011, 2(4), 223-228.
[http://dx.doi.org/10.4103/2229-4708.93390] [PMID: 23781461]
[http://dx.doi.org/10.4103/2229-4708.93390] [PMID: 23781461]
[14]
Roman, J.; Breier, A.R.; Steppe, M. Stability indicating LC method to determination of sodium montelukast in pharmaceutical dosage form and its photodegradation kinetics. J. Chromatogr. Sci., 2011, 49(7), 540-546.
[http://dx.doi.org/10.1093/chrsci/49.7.540] [PMID: 21801485]
[http://dx.doi.org/10.1093/chrsci/49.7.540] [PMID: 21801485]
[15]
Singh, R.M.; Saini, P.K.; Mathur, S.C.; Singh, G.N.; Lal, B. Development and validation of a RP-HPLC method for estimation of montelukast sodium in bulk and in tablet dosage form. Indian J. Pharm. Sci., 2010, 72(2), 235-237.
[http://dx.doi.org/10.4103/0250-474X.65023] [PMID: 20838530]
[http://dx.doi.org/10.4103/0250-474X.65023] [PMID: 20838530]
[16]
Pankhaniya, M.; Patel, P.; Shah, J.S. Stability-indicating HPLC method for simultaneous determination of montelukast and fexofenadine hydrochloride. Indian J. Pharm. Sci., 2013, 75(3), 284-290.
[http://dx.doi.org/10.4103/0250-474X.117426] [PMID: 24082344]
[http://dx.doi.org/10.4103/0250-474X.117426] [PMID: 24082344]
[17]
Wang, S.; Ni, X.J.; Wen, Y.G.; Xie, H.S.; Chen, J.R.; Luo, Y.L.; Li, P.L. A simple and sensitive HPLC-MS/MS assay for the quantitation of montelukast in cell-based systems in vitro pulmonary drug permeability study. J. Pharm. Biomed. Anal., 2021, 192, 113657.
[http://dx.doi.org/10.1016/j.jpba.2020.113657] [PMID: 33053506]
[http://dx.doi.org/10.1016/j.jpba.2020.113657] [PMID: 33053506]
[18]
Haghighi, S.; Shapouri, M.R.; Amoli-Diva, M.; Pourghazi, K.; Afruzi, H. HPTLC-densitometric determination of cetirizine and montelukast analysis in combined tablet dosage forms. Iran. J. Pharm. Res., 2013, 12(2), 303-309.
[PMID: 24250604]
[PMID: 24250604]
[19]
Abbas, M.; Khan, A.M.; Amin, S.; Riffat, S.; Ashraf, M.; Waheed, N. Bioequivalence study of montelukast tablets in healthy Pakistani volunteers. Pak. J. Pharm. Sci., 2013, 26(2), 255-259.
[PMID: 23455193]
[PMID: 23455193]
[20]
Bharathi, D.V.; Hotha, K.K.; Jagadeesh, B.; Mullangi, R.; Naidu, A. Quantification of montelukast, a selective cysteinyl leukotriene receptor (CysLT1) antagonist in human plasma by liquid chromatography-mass spectrometry: Validation and its application to a human pharmacokinetic study. Biomed. Chromatogr., 2009, 23(8), 804-810.
[http://dx.doi.org/10.1002/bmc.1189] [PMID: 19309765]
[http://dx.doi.org/10.1002/bmc.1189] [PMID: 19309765]
[21]
Cánovas, M.; Arcabell, M.; Martínez, G.; Canals, M.; Cabré, F. Bioequivalence studies of film-coated tablet and chewable tablet generic formulations of montelukast in healthy volunteers. Arzneimittelforschung, 2011, 61(11), 610-616.
[PMID: 22232849]
[PMID: 22232849]
[22]
Challa, B.R.; Awen, B.Z.; Chandu, B.R.; Khagga, M.; Kotthapalli, C.B. Method development and validation of montelukast in human plasma by HPLC coupled with ESI-MS/MS: Application to a bioequivalence study. Sci. Pharm., 2010, 78(3), 411-422.
[http://dx.doi.org/10.3797/scipharm.1002-07] [PMID: 21179354]
[http://dx.doi.org/10.3797/scipharm.1002-07] [PMID: 21179354]
[23]
Ezzeldin, E.; Abo-Talib, N.F.; Tammam, M.H.; Shahat, A.A. Development and validation of LC/MS/MS method for the simultaneous determination of montelukast, gliclazide, and nifedipine and its application to a pharmacokinetic study. Chem. Cent. J., 2014, 8(1), 17.
[http://dx.doi.org/10.1186/1752-153X-8-17] [PMID: 24618480]
[http://dx.doi.org/10.1186/1752-153X-8-17] [PMID: 24618480]
[24]
Ezzeldin, E.; Tammam, M.; AboTalib, N. Development of an LC-tandem mass spectrometry method for the separation of montelukast and its application to a pharmacokinetic study in humans. Drug Res. (Stuttg.), 2014, 64(11), 617-622.
[http://dx.doi.org/10.1055/s-0034-1366986] [PMID: 24500731]
[http://dx.doi.org/10.1055/s-0034-1366986] [PMID: 24500731]
[25]
Fey, C.; Thyroff-Friesinger, U.; Jones, S. Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults. Clin. Transl. Allergy, 2014, 4(1), 29.
[http://dx.doi.org/10.1186/2045-7022-4-29] [PMID: 25250173]
[http://dx.doi.org/10.1186/2045-7022-4-29] [PMID: 25250173]
[26]
Hassaninejad-Darzi, S.K.; Samadi-Maybodi, A.; Nikou, S.M. UV-Vis spectrophotometry and multivariate calibration method for simultaneous determination of theophylline, montelukast and loratadine in tablet preparations and spiked human plasma. Iran. J. Pharm. Res., 2016, 15(3), 379-391.
[PMID: 27980573]
[PMID: 27980573]
[27]
Knorr, B.; Hartford, A.; Li, X.S.; Yang, A.Y.; Noonan, G.; Migoya, E. Bioequivalence of the 4-mg oral granules and chewable tablet formulations of montelukast. Arch. Drug Inf., 2010, 3(2), 37-43.
[http://dx.doi.org/10.1111/j.1753-5174.2010.00029.x] [PMID: 20686624]
[http://dx.doi.org/10.1111/j.1753-5174.2010.00029.x] [PMID: 20686624]
[28]
Li, W.; Wang, Y.; Pei, Y.; Xia, Y. Pharmacokinetics and bioequivalence evaluation of two montelukast sodium chewable tablets in healthy Chinese volunteers under fasted and fed conditions. Drug Des. Devel. Ther., 2021, 15, 1091-1099.
[http://dx.doi.org/10.2147/DDDT.S298355] [PMID: 33727797]
[http://dx.doi.org/10.2147/DDDT.S298355] [PMID: 33727797]
[29]
Medina, A.P.; Olaya, F.J.; Navas, M.P.; Tilano, A.M.; Muñoz, E. Bioequivalence study of montelukast 5 mg chewable tablets. Biomédica, 2012, 32(3), 399-407.
[http://dx.doi.org/10.7705/biomedica.v32i3.708] [PMID: 23715188]
[http://dx.doi.org/10.7705/biomedica.v32i3.708] [PMID: 23715188]
[30]
Muppavarapu, R.; Guttikar, S.; Rajappan, M.; Kamarajan, K.; Mullangi, R. Sensitive LC-MS/MS-ESI method for simultaneous determination of montelukast and fexofenadine in human plasma: Application to a bioequivalence study. Biomed. Chromatogr., 2014, 28(8), 1048-1056.
[http://dx.doi.org/10.1002/bmc.3114] [PMID: 24424850]
[http://dx.doi.org/10.1002/bmc.3114] [PMID: 24424850]
[31]
Ahmed, S.; Atia, N.N. Simultaneous determination of montelukast as sparing therapy with some inhaled corticosteroids in plasma of asthmatic patients. J. Pharm. Biomed. Anal., 2013, 74, 250-256.
[http://dx.doi.org/10.1016/j.jpba.2012.11.004] [PMID: 23245258]
[http://dx.doi.org/10.1016/j.jpba.2012.11.004] [PMID: 23245258]
[32]
Zaid, A.N.; Abualhasan, M.; Watson, D.; Mousa, A.; Ghazal, N.; Bustami, R. Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method. Drug Des. Devel. Ther., 2015, 9, 5315-5321.
[http://dx.doi.org/10.2147/DDDT.S87938] [PMID: 26451086]
[http://dx.doi.org/10.2147/DDDT.S87938] [PMID: 26451086]
[33]
Ochiai, H.; Uchiyama, N.; Takano, T.; Hara, K.; Kamei, T. Determination of montelukast sodium in human plasma by column-switching high-performance liquid chromatography with fluorescence detection. J. Chromatogr., Biomed. Appl., 1998, 713(2), 409-414.
[http://dx.doi.org/10.1016/S0378-4347(98)00179-0] [PMID: 9746257]
[http://dx.doi.org/10.1016/S0378-4347(98)00179-0] [PMID: 9746257]
[34]
Smith, G.A.; Rawls, C.M.; Kunka, R.L. An automated method for the determination of montelukast in human plasma using dual-column HPLC analysis and peak height summation of the parent compound and its photodegradation product. Pharm. Res., 2004, 21(9), 1539-1544.
[http://dx.doi.org/10.1023/B:PHAM.0000041445.76931.27] [PMID: 15497676]
[http://dx.doi.org/10.1023/B:PHAM.0000041445.76931.27] [PMID: 15497676]
[35]
Sripalakit, P.; Kongthong, B.; Saraphanchotiwitthaya, A. A simple bioanalytical assay for determination of montelukast in human plasma: Application to a pharmacokinetic study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2008, 869(1-2), 38-44.
[http://dx.doi.org/10.1016/j.jchromb.2008.05.017] [PMID: 18508416]
[http://dx.doi.org/10.1016/j.jchromb.2008.05.017] [PMID: 18508416]
[36]
Sripalakit, P.; Maphanta, S.; Saraphanchotiwitthaya, A. Bioequivalence study of two generic formulations of 10 mg montelukast tablets in healthy Thai male volunteers. Int. J. Clin. Pharmacol. Ther., 2010, 48(9), 628-632.
[http://dx.doi.org/10.5414/CPP48628] [PMID: 20860917]
[http://dx.doi.org/10.5414/CPP48628] [PMID: 20860917]
[37]
Wong, E.Y.L.; Loh, G.O.K.; Tan, Y.T.F.; Peh, K.K. Development of LC-MS/MS method and application to bioequivalence study of a light sensitive drug montelukast. Drug Dev. Ind. Pharm., 2021, 47(2), 197-206.
[http://dx.doi.org/10.1080/03639045.2020.1862177] [PMID: 33300818]
[http://dx.doi.org/10.1080/03639045.2020.1862177] [PMID: 33300818]
[38]
Al-Rawithi, S.; Al-Gazlan, S.; Al-Ahmadi, W.; Alshowaier, I.A.; Yusuf, A.; Raines, D.A. Expedient liquid chromatographic method with fluorescence detection for montelukast sodium in micro-samples of plasma. J. Chromatogr., Biomed. Appl., 2001, 754(2), 527-531.
[http://dx.doi.org/10.1016/S0378-4347(01)00025-1] [PMID: 11339297]
[http://dx.doi.org/10.1016/S0378-4347(01)00025-1] [PMID: 11339297]
[39]
Ferreirós Bouzas, N.; Dresen, S.; Munz, B.; Weinmann, W. Determination of basic drugs of abuse in human serum by online extraction and LC–MS/MS. Anal. Bioanal. Chem., 2009, 395(8), 2499-2507.
[http://dx.doi.org/10.1007/s00216-009-3036-x] [PMID: 19701802]
[http://dx.doi.org/10.1007/s00216-009-3036-x] [PMID: 19701802]
[40]
Chan, P.K.; Dominic Chan, T-W. Effect of sample preparation methods on the analysis of dispersed polysaccharides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom., 2000, 14(19), 1841-1847.
[http://dx.doi.org/10.1002/1097-0231(20001015)14:19<1841::AID-RCM104>3.0.CO;2-Q] [PMID: 11006594]
[http://dx.doi.org/10.1002/1097-0231(20001015)14:19<1841::AID-RCM104>3.0.CO;2-Q] [PMID: 11006594]
[41]
Jiang, L.; He, L.; Fountoulakis, M. Comparison of protein precipitation methods for sample preparation prior to proteomic analysis. J. Chromatogr. A, 2004, 1023(2), 317-320.
[http://dx.doi.org/10.1016/j.chroma.2003.10.029] [PMID: 14753699]
[http://dx.doi.org/10.1016/j.chroma.2003.10.029] [PMID: 14753699]
[42]
Finoulst, I.; Pinkse, M.; Van Dongen, W.; Verhaert, P. Sample preparation techniques for the untargeted LC-MS-based discovery of peptides in complex biological matrices. J. Biomed. Biotechnol., 2011, 2011, 245291.
[http://dx.doi.org/10.1155/2011/245291] [PMID: 22203783]
[http://dx.doi.org/10.1155/2011/245291] [PMID: 22203783]
[43]
Henion, J.; Brewer, E.; Rule, G. Sample preparation for LC/MS/MS: Analyzing biological and environmental samples. Anal. Chem., 1998, 70(19), 650A-656A.
[http://dx.doi.org/10.1021/ac981991q] [PMID: 9784742]
[http://dx.doi.org/10.1021/ac981991q] [PMID: 9784742]
[44]
Villagrasa, M.; Guillamón, M.; Eljarrat, E.; Barceló, D. Matrix effect in liquid chromatography–electrospray ionization mass spectrometry analysis of benzoxazinoid derivatives in plant material. J. Chromatogr. A, 2007, 1157(1-2), 108-114.
[http://dx.doi.org/10.1016/j.chroma.2007.04.040] [PMID: 17507023]
[http://dx.doi.org/10.1016/j.chroma.2007.04.040] [PMID: 17507023]
[45]
Wu, J.; Qian, X.; Yang, Z.; Zhang, L. Study on the matrix effect in the determination of selected pharmaceutical residues in seawater by solid-phase extraction and ultra-high-performance liquid chromatography–electrospray ionization low-energy collision-induced dissociation tandem mass spectrometry. J. Chromatogr. A, 2010, 1217(9), 1471-1475.
[http://dx.doi.org/10.1016/j.chroma.2009.12.074] [PMID: 20074738]
[http://dx.doi.org/10.1016/j.chroma.2009.12.074] [PMID: 20074738]
[46]
Zhan, C.; Wang, C.; Wang, Y.; Xie, H.; Chu, J.; Zhang, R.; Hu, R.; Shen, J.; Jia, Y. Using a stable isotope‐labeled internal standard for liquid chromatography–tandem mass spectrometry quantitation of meloxicam in human plasma. Biomed. Chromatogr., 2021, 35(12), e5217.
[http://dx.doi.org/10.1002/bmc.5217] [PMID: 34405424]
[http://dx.doi.org/10.1002/bmc.5217] [PMID: 34405424]
[47]
Said, R.; Arafat, B.; Arafat, T. High performance liquid chromatography – Mass spectrometric bioanalytical method for the determination of dapoxetine in human plasma: Application for bioequivalence study. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2020, 1149, 122154.
[http://dx.doi.org/10.1016/j.jchromb.2020.122154] [PMID: 32485631]
[http://dx.doi.org/10.1016/j.jchromb.2020.122154] [PMID: 32485631]
