Trace Extraction of Metoprolol from Plasma, Urine and EBC Samples Using Modified Magnetic Nanoparticles Followed by Spectrofluorimetric Determination for Drug Monitoring Purposes

Author(s): Mohammad Ali Tarfiei, Ahad Bavili Tabrizi*, Abolghasem Jouyban

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 7 , 2020

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Graphical Abstract:


Background: Metoprolol is a selective β1-adrenergic receptor antagonist (β-blockers). It is widely used for the treatment of hypertension and other related diseases. Metoprolol can be used as a doping agent in sports, thus has been included in the list of forbidden drugs. In Iran, therapeutic drug monitoring (TDM) of β-blockers is an applied procedure in some cases. A therapeutic regimen could be easily managed by the determination of drug levels in biological fluids which is a relatively costly process and requires highly skilled technical staff. Using a simple and low-cost analytical procedure may help to use TDM in routine clinical practice.

Methods: A real biological sample was prepared and its pH was adjusted to 3-4, then metoprolol was quickly extracted using magnetic iron oxide nanoparticles (MIONPs) modified by sodium dodecyl sulfate (SDS) and determined by applying spectrofluorimetry at 340 ± 3 nm after excitation at 283 ± 3 nm.

Results: The extraction and determination conditions including, the amount of MIONPs and SDS, pH of the solution, standing time, desorption solvent type and volume were investigated and adjusted. Calibration curves were linear over the concentration range of 6–100 ng/mL for plasma and 5–100 ng/mL for water, urine and exhaled breath condensate samples, respectively. Intra and inter-day precision values for determination of metoprolol in different samples were less than 5.6 % and 6 %, respectively, and accuracy (as a relative error) was better than 5 %. Moreover, standard addition recovery tests were carried out, and the analytical recoveries ranged from 86 % to 113 %. The limits of detection (LOD) and limits of quantification (LOQ) of metoprolol were found to be in the range of 2.1-3.4 ng/mL and 6.3- 10.2 ng/mL, respectively.

Conclusion: The developed method was successfully applied to biological samples taken from a volunteer who was given an oral tablet of 50 mg metoprolol.

Keywords: Metoprolol, magnetic iron oxide nanoparticles, plasma, urine, exhaled breath condensate, spectrofluorimetry.

Desai, P. B.; Srivastava, A. K. Adsorptive stripping differential pulse voltammetric determination of metoprolol at Nafion-CNTnano-composite film sensor. sensor. actuat. b- chem., 2013, 176, 632-638.
Yilmaz, B.; Arslan, S.; Akba, V. Gas chromatography-mass spectrometry method for determination of metoprolol in the patients with hypertension. Talanta, 2009, 80(1), 346-351.
[] [PMID: 19782235]
Grassi, G. Metoprolol in the treatment of cardiovascular disease: a critical reappraisal. Curr. Med. Res. Opin., 2018, 34(9), 1635-1643.
[] [PMID: 29781321]
Chen, Y.Y.; Yang, W.P.; Zhang, Z.J. Determination of metoprolol in rabbit blood using capillary electrophoresis with laser-induced fluorescence detection. Chin. Chem. Lett., 2011, 22(3), 350-353.
Jung, O.; Gechter, J.L.; Wunder, C.; Paulke, A.; Bartel, C.; Geiger, H.; Toennes, S.W. Resistant hypertension? Assessment of adherence by toxicological urine analysis. J. Hypertens., 2013, 31(4), 766-774.
[] [PMID: 23337469]
Brinker, S.; Pandey, A.; Ayers, C.; Price, A.; Raheja, P.; Arbique, D.; Das, S.R.; Halm, E.A.; Kaplan, N.M.; Vongpatanasin, W. Therapeutic drug monitoring facilitates blood pressure control in resistant hypertension. J. Am. Coll. Cardiol., 2014, 63(8), 834-835.
[] [PMID: 24315901]
Mancia, G.; Fagard, R.; Narkiewicz, K.; Redán, J.; Zanchetti, A.; Böhm, M.; Christiaens, T.; Cifkova, R.; De Backer, G.; Dominiczak, A. ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC task force for the management of arterial hypertension. J. Hypertens., 2013, 31(10), 1925-1938.
[] [PMID: 24107724]
Xu, T.; Bao, S.; Geng, P.; Luo, J.; Yu, L.; Pan, P.; Chen, Y.; Hu, G. Determination of metoprolol and its two metabolites in human plasma and urine by high performance liquid chromatography with fluorescence detection and its application in pharmacokinetics. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2013, 937, 60-66.
[] [PMID: 24018320]
Baranowska, I.; Adolf, W.; Magiera, S. Enantioselective determination of metoprolol and its metabolites in human urine highperformance liquid chromatography with fluorescence detection (HPLC-FLD) and tandem mass spectrometry (MS/MS). J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2015, 1004, 79-84.
[] [PMID: 26451466]
Hemmati, M.; Asghari, A.; Bazregar, M.; Rajabi, M. Rapid determination of some beta-blockers in complicated matrices by tandem dispersive liquid-liquid microextraction followed by high performance liquid chromatography. Anal. Bioanal. Chem., 2016, 408(28), 8163-8176.
[] [PMID: 27734141]
Magiera, S.; Kolanowska, A.; Baranowski, J. Salting-out assisted extraction method coupled with hydrophilic interaction liquid chromatography for determination of selected β-blockers and their metabolites in human urine. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2016, 1022, 93-101.
[] [PMID: 27085018]
Chiu, F.C.K.; Damani, L.A.; Li, R.C.; Tomlinson, B. Efficient high-performance liquid chromatographic assay for the simultaneous determination of metoprolol and two main metabolites in human urine by solid-phase extraction and fluorescence detection. J. Chromatogr. B Biomed. Sci. Appl., 1997, 696(1), 69-74.
[] [PMID: 9300910]
Yilmaz, B.; Asci, A.; Arslan, S. Determination of metoprolol in human plasma and urine by high-performance liquid chromatography with fluorescence detection. J. Sep. Sci., 2010, 33(13), 1904-1908.
[] [PMID: 20512810]
Hemmati, M.; Rajabi, M.; Asghari, A. Ultrasound-promoted dispersive micro solid-phase extraction of trace anti-hypertensive drugs from biological matrices using a sonochemically synthesized conductive polymer nanocomposite. Ultrason. Sonochem., 2017, 39, 12-24.
[] [PMID: 28732927]
Zoerner, A.A.; Schroeder, C.; Kayacelebi, A.A.; Suchy, M.T.; Gutzki, F-M.; Stichtenoth, D.O.; Tank, J.; Jordan, J.; Tsikas, D. A validated, rapid UPLC-MS/MS method for simultaneous ivabradine, reboxetine, and metoprolol analysis in human plasma and its application to clinical trial samples. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2013, 927, 105-111.
[] [PMID: 23434314]
Xiao, X.; Zhang, M-M.; Wang, Z-Q. Determination of β-blockers in bovine and porcine tissues and bovine milk by high-performance liquid chromatography–tandem mass spectrometry. Anal. Lett., 2018, 1-13.
Rodina, T.A.; Mel’nikov, E.S.; Dmitriev, A.I.; Belkov, S.A.; Sokolov, A.V.; Arkhipov, V.V.; Prokof’ev, A.B. Simultaneous determination of metoprolol and bisoprolol in human serum by HPLCMS/MS for clinical drug monitoring. Pharm. Chem. J., 2018, 51(12), 1111-1118.
Chen, M.; Zhou, J.; Mei, L.; Yu, F.; Xie, X.; Liu, Y.; Yang, Y.; Li, Y.; Mei, X. Simultaneous determination of felodipine and metoprolol in beagle dog plasma by online SPE-LC-MS/MS and its application in a pharmacokinetic study. Anal. Sci., 2017, 33(7), 755-759.
[] [PMID: 28690250]
Sun, S.; Wang, Y.; Liu, X.; Fu, R.; Yang, L. Rapid and sensitive tapered-capillary microextraction combined to on-line sample stacking-capillary electrophoresis for extraction and quantification of two beta-blockers in human urine. Talanta, 2018, 180, 90-97.
[] [PMID: 29332838]
Silva, M.; Morante-Zarcero, S.; Pérez-Quintanilla, D.; Marina, M.L.; Sierra, I. Preconcentration of β-blockers using functionalized ordered mesoporous silica as sorbent for SPE and their determination in waters by chiral CE. Electrophoresis, 2017, 38(15), 1905-1912.
[] [PMID: 28369986]
Salamanca-Neto, C. A. R.; Eisele, A. P. P.; Resta, V. G.; Scremin, J.; Sartori, E. R. Differential pulse voltammetric method for the individual and simultaneous determination of antihypertensive drug metoprolol and its association with hydrochlorothiazide in pharmaceutical dosage forms. Talanta , 2016, 80(1), 346-351.
Er, E.; Çelikkan, H.; Erk, N. a novel electrochemical nanoplatform based on gra-phene/platinum nanoparticles/nafion composites for the electrochemical sensing of metoprolol. sensor. actuat. b- chem, 2017, 238, 779-787.
Huang, X.; Xie, L.; Lin, X.; Su, B. Detection of metoprolol in human biofluids and pharmaceuticals via ion-transfer voltammetry at the nanoscopic liquid/liquid interface array. Anal. Chem., 2017, 89(1), 945-951.
[] [PMID: 27958719]
Zhang, Y.; Wu, H-L.; Xia, A-L.; Zhu, S-H.; Han, Q-J.; Yu, R-Q. Fluorescence determination of metoprolol in human plasma by trilinear decomposition-based calibration techniques. Anal. Bioanal. Chem., 2006, 386(6), 1741-1748.
[] [PMID: 17047945]
Soltani, S.; Jouyban, A. A validated micellar LC method for simultaneous determination of furosemide, metoprolol and verapamil in human plasma. Bioanalysis, 2012, 4(1), 41-48.
[] [PMID: 22191593]
Yamini, Y.; Faraji, M. Extraction and determination of trace amounts of chlorpromazine in biological fluids using magnetic solid phase extraction followed by HPLC. J. Pharm. Anal., 2014, 4(4), 279-285.
[] [PMID: 29403891]
Bavili Tabrizi, A.; Rashidi, M.R.; Ostadi, H. A nanoparticle-based solid-phase extraction procedure followed by spectrofluorimetry to determine carbaryl in different water samples. J. Braz. Chem. Soc., 2014, 25(4), 709-715.
Wu, J.; Zhao, H.; Xiao, D.; Chuong, P-H.; He, J.; He, H. Mixed hemimicelles solid-phase extraction of cephalosporins in biological samples with ionic liquid-coated magnetic graphene oxide nanoparticles coupled with high-performance liquid chromatographic analysis. J. Chromatogr. A, 2016, 1454, 1-8.
[] [PMID: 27266334]
Vasconcelos, I.; Fernandes, C. Magnetic solid phase extraction for determination of drugs in biological matrices. TrAC-Trend. Anal. Chem., 2017, 89, 41-52.
Bavili Tabrizi, A.; Dehghani Teymurlouie, N. Application of sodium dodecyl sulfate coated iron oxide magnetic nanoparticles for the extraction and spectrofluorimetric determination of propranolol in different biological samples. J. Mex. Chem. Soc., 2016, 60(3), 108-116.
Pérez, R.A.; Albero, B.; Tadeo, J.L.; Sánchez-Brunete, C. Determination of endocrine-disrupting compounds in water samples by magnetic nanoparticle-assisted dispersive liquid-liquid microextraction combined with gas chromatography-tandem mass spectrometry. Anal. Bioanal. Chem., 2016, 408(28), 8013-8023.
[] [PMID: 27614975]
Esmaeili-Shahri, E.; Es’haghi, Z. Superparamagnetic Fe3 O4 @SiO2 core-shell composite nanoparticles for the mixed hemimicelle solid-phase extraction of benzodiazepines from hair and wastewater samples before high-performance liquid chromatography analysis. J. Sep. Sci., 2015, 38(23), 4095-4104.
[] [PMID: 26412451]
Wang, L.; Yuan, Q.; Liang, G.; Shi, L.; Zhan, Q. Magnetic mixed hemimicelles solid-phase extraction coupled with highperformance liquid chromatography for the extraction and rapid determination of six fluoroquinolones in environmental water samples. J. Sep. Sci., 2015, 38(6), 996-1001.
[] [PMID: 25581496]
Baciu, T.; Borrull, F.; Neusüß, C.; Aguilar, C.; Calull, M. Capillary electrophoresis combined in-line with solid-phase extraction using magnetic particles as new adsorbents for the determination of drugs of abuse in human urine. Electrophoresis, 2016, 37(9), 1232-1244.
[] [PMID: 26856766]
Mukdasai, S.; Butwong, N.; Thomas, C.; Srijaranai, S.; Srijaranai, S. A sensitive and selective spectrophotometric method for 2-chlorophenol based on solid phase extraction with mixed hemimicelle magnetic nanoparticles. Arab. J. Chem., 2016, 9(3), 463-470.
Yang, X.; Qiao, K.; Liu, F.; Wu, X.; Yang, M.; Li, J.; Gao, H.; Zhang, S.; Zhou, W.; Lu, R. Magnetic mixed hemimicelles dispersive solid-phase extraction based on ionic liquid-coated attapulgite/polyaniline-polypyrrole/Fe3O4 nanocomposites for determination of acaricides in fruit juice prior to high-performance liquid chromatography-diode array detection. Talanta, 2017, 166, 93-100.
[] [PMID: 28213265]
Khalilian, F.; Rezaee, M. Mixed-hemimicelle solid phase extraction followed by dispersive liquid-liquid microextraction of amphetamines from biological samples. J. Brazil. Chem. Soc., 2016, 27(11), 2105-2113.
Bavili Tabrizi, A.; Panahi, M. Solid phase extraction using modified magnetic iron oxide nanoparticles for extraction and spectrofluorimetric determination of carvedilol in human plasma samples. Iran. J. Chem. Chem. Eng., 2017, 36(3), 115-125.
Pérez, R.A.; Albero, B.; Tadeo, J.L.; Molero, E.; Sánchez-Brunete, C. Application of magnetic iron oxide nanoparticles for the analysis of PCBs in water and soil leachates by gas chromatography-tandem mass spectrometry. Anal. Bioanal. Chem., 2015, 407(7), 1913-1924.
[] [PMID: 25644520]
Li, P.; Pei, F.; Liu, Q.; Fang, Y. Magnetic solid-phase extraction for the determination of ochratoxin A in wine and beer by HPLCFLD. Curr. Anal. Chem., 2018, 14(2), 129-134.
Zhang, H-F.; Shi, Y-P. Pretreatment properties of CTAB coated Fe3O4 nanoparticle mixed hemimicelle sorbents for the analysis of herbal medicine samples. Curr. Anal. Chem., 2012, 8(1), 150-158.
Bavili Tabrizi, A.; Sepehr, B. Extraction of ammonia and nitrite using modified magnetite iron oxide nanoparticles before spectrophotometric determination in different water samples. Int. J. Environ. Anal. Chem., 2015, 95(9), 833-846.
Moradian, M.; Moradian, M.; Boroumand, Z. A new and efficient method for the adsorption and separation of arsenic metal ion from mining Waste Waters of Zarshouran Gold Mine by Magnetic SolidPhase extraction with modified magnetic nanoparticles. Nanosci. Nanotechnol., 2013, 9(3), 121-126.
Yin, Q.; Zhu, Y.; Ju, S.; Liao, W.; Yang, Y. Rapid determination of copper and lead in Panax notoginseng by magnetic solid-phase extraction and flame atomic absorption spectrometry. Res. Chem. Intermed., 2016, 42(5), 4985-4998.
Wei, Z.; Sandron, S.; Townsend, A.T.; Nesterenko, P.N.; Paull, B. Determination of trace labile copper in environmental waters by magnetic nanoparticle solid phase extraction and high-performance chelation ion chromatography. Talanta, 2015, 135, 155-162.
[] [PMID: 25640140]
Vereda Alonso, E.; Guerrero, Mdel.M.; Colorado Cueto, P.; Barreno Benítez, J.; Cano Pavón, J.M.; García de Torres, A. Development of an on-line solid phase extraction method based on new functionalized magnetic nanoparticles. Use in the determination of mercury in biological and sea-water samples. Talanta, 2016, 153, 228-239.
[] [PMID: 27130113]
Mahmoud, M.E.; Amira, M.F.; Zaghloul, A.A.; Ibrahim, G.A.A. Microwave-enforced sorption of heavy metals from aqueous solutions on the surface of magnetic iron oxide-functionalized-3-aminopropyltriethoxysilane. Chem. Eng. J., 2016, 293, 200-206.
López-García, I.; Rengevicova, S.; Muñoz-Sandoval, M.J.; Hernández-Córdoba, M. Speciation of very low amounts of antimony in waters using magnetic core-modified silver nanoparticles and electrothermal atomic absorption spectrometry. Talanta, 2017, 162, 309-315.
[] [PMID: 27837834]
Tavallali, H.; Deilamy-Rad, G.; Peykarimah, P. Preconcentration and speciation of Cr(III) and Cr(VI) in water and soil samples by spectrometric detection via use of nanosized alumina-coated magnetite solid phase. Environ. Monit. Assess., 2013, 185(9), 7723-7738.
[] [PMID: 23430069]
Faraji, M.; Yamini, Y.; Rezaee, M. Magnetic nanoparticles: synthesis, stabilization, functionalization, characterization, and applications. J. Iran. Chem. Soc., 2010, 7(1), 1-37.
Samadi Kazemi, M. Solid phase extraction based on thiol functionalized magnetite nanoparticles to determination some heavy metal ions in water samples using atomic absorption spectrometry. Curr. Anal. Chem., 2017, 13(2), 174-180.
Filik, H. Aslihan Avan, Asiye. Ionic liquid based dispersive liquidliquid microextraction combined with magnetic-based dispersive micro-solid-phase extraction for determination of trace cobalt in water samples by FAAS. Curr. Anal. Chem., 2017, 13(6), 456-463.
Khoubnasabjafari, M.; Rahimpour, E.; Jouyban, A. Exhaled breath condensate as an alternative sample for drug monitoring. Bioanalysis, 2018, 10(2), 61-64.
[] [PMID: 29236512]
Rahimpour, E.; Khoubnasabjafari, M.; Jouyban-Gharamaleki, V.; Jouyban, A. Non-volatile compounds in exhaled breath condensate: review of methodological aspects. Anal. Bioanal. Chem., 2018, 410(25), 6411-6440.
[] [PMID: 30046867]
Jouyban, A.; Khoubnasabjafari, M.; Ansarin, K.; Jouyban-Gharamaleki, V. Breath sampling setup. iranian patent,, 2013,.81363.,
Hasanzadeh, M.; Zamani-Kalajahi, M.; Shadjou, N.; Khoubnasabjafari, M.; Ansarin, K.; Jouyban-Gharamaleki, V.; Jouyban, A. Electrodeposition of taurine on a gold electrode for electrooxidation of malondialdehyde in human serum and exhaled breath condensate. Surf. Eng., 2015, 31(3), 194-201.
Khoubnasabjafari, M.; Ansarin, K.; Jouyban-Gharamaleki, V.; Panahi-Azar, V.; Shayanfar, A.; Mohammadzadeh, L.; Jouyban, A. Extraction and analysis of methadone in exhaled breath condensate using a validated HPLC-UV method. J. Pharm. Pharm. Sci., 2015, 18(2), 207-219.
[] [PMID: 26158286]
Jouyban, A.; Samadi, A.; Khoubnasabjafari, M.; JouybanGharamaleki, V.; Ranjbar, F. Amidosulfonic acid capped silver nanoparticles as a new spectrophotometric probe for rapid quantification of lamotrigine in exhaled breath condensate. Mikrochim. Acta, 2017, 184(8), 2991-2998.
Hamidi, S.; Amini, M.; Khoubnasabjafari, M.; Jouyban-Gharamaleki, V.; Sate, H.; Jouyban, A. LC-MS determination of propranolol in exhaled breath condensate. Pharm. Sci., 2017, 23, 264-270.
Tabrizi, A.B.; Naini, S.; Parnian, K.; Mohammadi, S. Emami zad, F.; Anvarian, S. P.; Abdollahi, A. Determination of triamterene in human plasma and urine after its cloud point extraction. Quim. Nova, 2014, 37(7), 1182-1187.
Sepehr, B.; Bavili-Tabrizi, A.; Jouyban-Gharamaleki, V.; Khoubnasabjafari, M.; Jouyban, A. A sensitive determination of ammonia and nitrite in exhaled breath condensate of healthy humans by using berthelot reaction. Curr. Pharm. Anal., 2018, 14(6), 555-561.
Pourkarim, F.; Rahimpour, E.; Khoubnasabjafari, M.; Jouyban-Gharamaleki, V.; Jouyban, A. Direct monitoring of verapamil level in exhaled breath condensate samples. Pharm. Sci., in press
Hatefi, A.; Rahimpour, E.; Khoubnasabjafari, M.; Edalat, M.; Jouyban-Gharamaleki, V.; Alvani-Alamdari, S.; Nokhodchi, A.; Pournaghi-Azar, M.H.; Jouyban, A. A single-shot diagnostic platform based on copper nanoclusters coated with cetyl trimethylammonium bromide for determination of carbamazepine in exhaled breath condensate. Mikrochim. Acta, 2019, 186(3), 194.
[] [PMID: 30778721]
Hamidi, S.; Khoubnasabjafari, M.; Ansarin, K.; JouybanGharamaleki, V.; Jouyban, A. Direct analysis of methadone in exhaled breath condensate by capillary zone electrophoresis. Curr. Pharm. Anal., 2016, 12, 137-145.
Jouyban, A.; Rahimpour, E.; Abdolmohamad-Zadeh, H.; Khoubnasabjafari, M.; Jouyban-Gharamaleki, V. A novel fluorometric sensor for hydrogen peroxide monitoring in exhaled breath condensate. Anal. Methods, 2017, 9, 4371-4379.
Mohamadian, E.; Shayanfar, A.; Khoubnasabjafari, M.; Jouyban-Gharamaleki, V.; Ghaffary, S.; Jouyban, A. Analysis of deferiprone in exhaled breath condensate using silver nanoparticles enhanced terbium fluorescence. Anal. Methods, 2017, 9, 5640-5645.
FDA; guidance for industry: bioanalytical method valida-tion. us department of health and human services. food and drug administration, center for drug evaluation and research, center for veterinary medicine, 2015 , 2015.
Caban, M.; Stepnowski, P.; Kwiatkowski, M.; Migowska, N.; Kumirska, J. Determination of β-blockers and β-agonists using gas chromatography and gas chromatography-mass spectrometry--a comparative study of the derivatization step. J. Chromatogr. A, 2011, 1218(44), 8110-8122.
[] [PMID: 21945621]
Jouyban, A.; Sorouraddin, M.H.; Farajzadeh, M.A.; Somi, M.H.; Fazeli-Bakhtiyari, R. Determination of five antiarrhythmic drugs in human plasma by dispersive liquid-liquid microextraction and high-performance liquid chromatography. Talanta, 2015, 134, 681-689.
[] [PMID: 25618722]
Johannsen, J-O.; Reuter, H.; Hoffmann, F.; Blaich, C.; Wiesen, M.H.J.; Streichert, T.; Müller, C. Reliable and easy-to-use LCMS/MS-method for simultaneous determination of the antihypertensives metoprolol, amlodipine, canrenone and hydrochlorothiazide in patients with therapy-refractory arterial hypertension. J. Pharm. Biomed. Anal., 2019, 164, 373-381.
[] [PMID: 30439665]

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Year: 2020
Published on: 28 March, 2019
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DOI: 10.2174/1573412915666190328212231
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