{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:25:07Z","timestamp":1775798707720,"version":"3.50.1"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"20","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["LA\/P\/0008\/2020 DOI 10.54499\/LA\/P\/0008\/2020"],"award-info":[{"award-number":["LA\/P\/0008\/2020 DOI 10.54499\/LA\/P\/0008\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/5"],"award-info":[{"award-number":["UIDP\/5"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/146999\/2019"],"award-info":[{"award-number":["SFRH\/BD\/146999\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2022.11168"],"award-info":[{"award-number":["2022.11168"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2023.00262.BD"],"award-info":[{"award-number":["2023.00262.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDP\/04423\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006752","name":"Universidade do Porto","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006752","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Anal Bioanal Chem"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\u201cPurple Drank\u201d, a soft drink containing promethazine (PMZ) and codeine (COD), has gained global popularity for its hallucinogenic effects. Consuming large amounts of this combination can lead to potentially fatal events. The binding of these drugs to plasma proteins can exacerbate the issue by increasing the risk of drug interactions, side effects, and\/or toxicity. Herein, the binding affinity to human serum albumin (HSA) of PMZ and its primary metabolites [<jats:italic>N<\/jats:italic>-desmethyl promethazine (DMPMZ) and promethazine sulphoxide (PMZSO)], along with COD, was investigated by high-performance affinity chromatography (HPAC) though zonal approach. PMZ and its metabolites exhibited a notable binding affinity for HSA (%<jats:italic>b<\/jats:italic> values higher than 80%), while COD exhibited a %<jats:italic>b<\/jats:italic> value of 65%. To discern the specific sites of HSA to which these compounds were bound, displacement experiments were performed using warfarin and (<jats:italic>S<\/jats:italic>)-ibuprofen as probes for sites I and II, respectively, which revealed that all analytes were bound to both sites. Molecular docking studies corroborated the experimental results, reinforcing the insights gained from the empirical data. The in silico data also suggested that competition between PMZ and its metabolites with COD can occur in both sites of HSA, but mainly in site II. As the target compounds are chiral, the enantioselectivity for HSA binding was also explored, showing that the binding for these compounds was not enantioselective.<\/jats:p>","DOI":"10.1007\/s00216-024-05409-3","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T16:01:58Z","timestamp":1720108918000},"page":"4605-4618","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Binding studies of promethazine and its metabolites with human serum albumin by high-performance affinity chromatography and molecular docking in the presence of codeine"],"prefix":"10.1007","volume":"416","author":[{"given":"Maria Miguel","family":"Coelho","sequence":"first","affiliation":[]},{"given":"Rita","family":"Lima","sequence":"additional","affiliation":[]},{"given":"Ana Sofia","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"Pedro Alexandrino","family":"Fernandes","sequence":"additional","affiliation":[]},{"given":"Fernando","family":"Remi\u00e3o","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0940-9163","authenticated-orcid":false,"given":"Carla","family":"Fernandes","sequence":"additional","affiliation":[]},{"given":"Maria Elizabeth","family":"Tiritan","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,7,4]]},"reference":[{"key":"5409_CR1","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1177\/026988112095","volume":"35","author":"S Chiappini","year":"2021","unstructured":"Chiappini S, Schifano F, Corkery JM, Guirguis A. Beyond the \u2018purple drank\u2019: study of promethazine abuse according to the european medicines agency adverse drug reaction reports. J Psychopharmacol. 2021;35:681\u201392. https:\/\/doi.org\/10.1177\/026988112095.","journal-title":"J Psychopharmacol"},{"key":"5409_CR2","doi-asserted-by":"publisher","first-page":"3497045","DOI":"10.1155\/2019\/3497045","volume":"2019","author":"S Gao","year":"2019","unstructured":"Gao S, Zhou X, Lang L, Liu H, Li J, Li H, Wei S, Wang D, Xu Z, Cai H, Zhao Y, Zou W. Simultaneous determination of schisandrin and promethazine with its metabolite in rat plasma by HPLC-MS\/MS and its application to a pharmacokinetic study. Int J Anal Chem. 2019;2019:3497045. https:\/\/doi.org\/10.1155\/2019\/3497045.","journal-title":"Int J Anal Chem"},{"key":"5409_CR3","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1080\/02791072.2020.1797250","volume":"52","author":"A Miuli","year":"2020","unstructured":"Miuli A, Stigliano G, Lalli A, Coladonato M, D\u2019Angelo L, Esposito F, Cappello C, Pettorruso M, Martinotti G, Schifano F, Di Giannantonio M. \u201cPurple drank\u201d (codeine and promethazine cough syrup): a systematic review of a social phenomenon with medical implications. J Psychoact Drugs. 2020;52:453\u201362. https:\/\/doi.org\/10.1080\/02791072.2020.1797250.","journal-title":"J Psychoact Drugs"},{"key":"5409_CR4","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1093\/chromsci\/39.2.70","volume":"39","author":"SR Vanapalli","year":"2001","unstructured":"Vanapalli SR, Kambhampati SP, Putcha L, Bourne DWA. A liquid chromatographic method for the simultaneous determination of promethazine and three of its metabolites in plasma using electrochemical and uv detectors. J Chromatogr Sci. 2001;39:70\u20132. https:\/\/doi.org\/10.1093\/chromsci\/39.2.70.","journal-title":"J Chromatogr Sci"},{"key":"5409_CR5","doi-asserted-by":"publisher","unstructured":"Coelho MM, Costa I, de Albuquerque ACF, dos Santos Junior FM, Silva B, Silva R, Fernandes C, Remi\u00e3o F, Tiritan ME (2024) Milligram scale enantioresolution of promethazine and its main metabolites, determination of their absolute configuration and assessment of enantioselective effects on human SY-SY5Y cells. J Pharmaceut Biomed. 245. https:\/\/doi.org\/10.1016\/j.jpba.2024.116152.","DOI":"10.1016\/j.jpba.2024.116152"},{"key":"5409_CR6","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1016\/j.addbeh.2013.03.020","volume":"38","author":"LE Agnich","year":"2013","unstructured":"Agnich LE, Stogner JM, Miller BL, Marcum CD. Purple drank prevalence and characteristics of misusers of codeine cough syrup mixtures. Addict Behav. 2013;38:2445\u20139. https:\/\/doi.org\/10.1016\/j.addbeh.2013.03.020.","journal-title":"Addict Behav"},{"key":"5409_CR7","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.2190\/NXJ6-U60J-XTY0-09MP","volume":"44","author":"RJ Peters Jr","year":"2003","unstructured":"Peters RJ Jr, Kelder SH, Markham CM, Yacoubian GS Jr, Peters LA, Ellis A. Beliefs and social norms about codeine and promethazine hydrochloride cough syrup (Cphcs) onset and perceived addiction among urban houstonian adolescents: an addiction trend in the city of lean. J Org Chem. 2003;44:1957\u201360. https:\/\/doi.org\/10.2190\/NXJ6-U60J-XTY0-09MP.","journal-title":"J Org Chem"},{"key":"5409_CR8","unstructured":"Dean L, Kane M. Codeine therapy and CYP2D6 genotype. Europe PMC. 2021."},{"key":"5409_CR9","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.drugalcdep.2015.02.023","volume":"150","author":"KL Lynch","year":"2015","unstructured":"Lynch KL, Shapiro BJ, Coffa D, Novak SP, Kral AH. Promethazine use among chronic pain patients. Drug Alcohol Depend. 2015;150:92\u20137. https:\/\/doi.org\/10.1016\/j.drugalcdep.2015.02.023.","journal-title":"Drug Alcohol Depend"},{"key":"5409_CR10","first-page":"276","volume":"17","author":"BR Overholser","year":"2011","unstructured":"Overholser BR, Foster DR. Opioid pharmacokinetic drug-drug interactions. AJMC. 2011;17:276\u201387.","journal-title":"AJMC"},{"key":"5409_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/molecules26113113","volume":"26","author":"MM Coelho","year":"2021","unstructured":"Coelho MM, Fernandes C, Remi\u00e3o F, Tiritan ME. Enantioselectivity in drug pharmacokinetics and toxicity: pharmacological relevance and analytical methods. Molecules. 2021;26:1\u201324. https:\/\/doi.org\/10.3390\/molecules26113113.","journal-title":"Molecules"},{"key":"5409_CR12","doi-asserted-by":"publisher","unstructured":"Rowland M, Matin SB (1973) Kinetics of drug-drug interactions J Pharmacokinet Biopharm. 1. https:\/\/doi.org\/10.1007\/BF01059791.","DOI":"10.1007\/BF01059791"},{"key":"5409_CR13","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.2174\/0929867023369673","volume":"9","author":"C Bertucci","year":"2002","unstructured":"Bertucci C, Domenici E. Reversible and covalent binding of drugs to human serum albumin: methodological approaches and physiological relevance. Curr Med Chem. 2002;9:1463\u201381. https:\/\/doi.org\/10.2174\/0929867023369673.","journal-title":"Curr Med Chem"},{"key":"5409_CR14","doi-asserted-by":"publisher","first-page":"416","DOI":"10.2165\/00003088-199630060-00002","volume":"30","author":"S Harder","year":"1996","unstructured":"Harder S, Thurmann P. Clinically important drug interactions with anticoagulants. Clin Pharmacokinet. 1996;30:416\u201344. https:\/\/doi.org\/10.2165\/00003088-199630060-00002.","journal-title":"Clin Pharmacokinet"},{"key":"5409_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40262-012-0018-5","volume":"52","author":"JA Roberts","year":"2013","unstructured":"Roberts JA, Pea F, Lipman J. The clinical relevance of plasma protein binding changes. Clin Pharmacokinet. 2013;52:1\u20138. https:\/\/doi.org\/10.1007\/s40262-012-0018-5.","journal-title":"Clin Pharmacokinet"},{"issue":"9","key":"5409_CR16","doi-asserted-by":"publisher","first-page":"2953","DOI":"10.1002\/jps.23614","volume":"102","author":"T Bohnert","year":"2013","unstructured":"Bohnert T, Gan LS. Plasma protein binding: from discovery to development. J Pharm Sci. 2013;102(9):2953\u201394. https:\/\/doi.org\/10.1002\/jps.23614.","journal-title":"J Pharm Sci"},{"key":"5409_CR17","doi-asserted-by":"crossref","unstructured":"Mehvar R. Role of protein binding in pharmacokinetics. Am J Pharm Educ. 2005;69(5).","DOI":"10.5688\/aj69051526"},{"key":"5409_CR18","doi-asserted-by":"publisher","first-page":"743","DOI":"10.2174\/0929867324666161118115711","volume":"24","author":"C Bertucci","year":"2017","unstructured":"Bertucci C, Tedesco D. Human serum albumin as chiral selector in enantioselective high-performance liquid chromatography. Curr Med Chem. 2017;24:743\u201357. https:\/\/doi.org\/10.2174\/0929867324666161118115711.","journal-title":"Curr Med Chem"},{"key":"5409_CR19","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jpba.2017.01.026","volume":"144","author":"Z Li","year":"2017","unstructured":"Li Z, Hage DS. Analysis of stereoselective drug interactions with serum proteins by high-performance affinity chromatography: a historical perspective. J Pharm Biomed Anal. 2017;144:12\u201324. https:\/\/doi.org\/10.1016\/j.jpba.2017.01.026.","journal-title":"J Pharm Biomed Anal"},{"key":"5409_CR20","doi-asserted-by":"publisher","unstructured":"Cardoso T, Almeida AS, Remi\u00e3o F, Fernandes C (2021) Enantioresolution and binding affinity studies on human serum albumin: recent applications and trends. Chemosensors. 9. https:\/\/doi.org\/10.3390\/chemosensors9110304.","DOI":"10.3390\/chemosensors9110304"},{"key":"5409_CR21","doi-asserted-by":"publisher","unstructured":"Siddiqui S, Ameen F, Rehman S, Sarwar T, Tabish M (2021) Studying the interaction of drug\/ligand with serum albumin. J Mol Liq. 336. https:\/\/doi.org\/10.1016\/j.molliq.2021.116200.","DOI":"10.1016\/j.molliq.2021.116200"},{"key":"5409_CR22","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.2174\/1381612824666180808145320","volume":"24","author":"K Wanat","year":"2018","unstructured":"Wanat K, Brzezi\u0144ska E, Soba\u0144ska AW. Aspects of drug-protein binding and methods of analyzing the phenomenon. Curr Pharm Des. 2018;24:2974\u201385. https:\/\/doi.org\/10.2174\/1381612824666180808145320.","journal-title":"Curr Pharm Des"},{"key":"5409_CR23","doi-asserted-by":"publisher","unstructured":"Rodriguez EL, Poddar S, Iftekhar S, Suh K, Woolfork AG, Ovbude S, Pekarek A, Walters M, Lott S, Hage DS (2020) Affinity chromatography: a review of trends and developments over the past 50 years. J Chromatogr B Biomed Appl. 1157. https:\/\/doi.org\/10.1016\/j.jchromb.2020.122332.","DOI":"10.1016\/j.jchromb.2020.122332"},{"key":"5409_CR24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2023.123836","author":"AS Almeida","year":"2023","unstructured":"Almeida AS, Cardoso T, Cravo S, Tiritan ME, Remi\u00e3o F, Fernandes C. Binding studies of synthetic cathinones to human serum albumin by high-performance affinity chromatography. J Chromatogr B Biomed Appl. 2023. https:\/\/doi.org\/10.1016\/j.jchromb.2023.123836.","journal-title":"J Chromatogr B Biomed Appl"},{"key":"5409_CR25","doi-asserted-by":"publisher","unstructured":"Ovbude ST, Tao P, Li Z, Hage DS (2022) Characterization of binding by repaglinide and nateglinide with glycated human serum albumin using high-performance affinity microcolumns. J Sep Sci. 45(23). https:\/\/doi.org\/10.1002\/jssc.202200686.","DOI":"10.1002\/jssc.202200686"},{"key":"5409_CR26","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S0378-4347(01)00493-5","volume":"768","author":"V Andrisano","year":"2002","unstructured":"Andrisano V, Gotti R, Recanatini M, Cavalli A, Varoli L, Bertucci C. Stereoselective binding of 2-(4-biphenylyl)-3-substituted-3-hydroxypropionic acids on an immobilised human serum albumin chiral stationary phase. J Chromatogr B Biomed Appl. 2002;768:137\u201345. https:\/\/doi.org\/10.1016\/S0378-4347(01)00493-5.","journal-title":"J Chromatogr B Biomed Appl"},{"issue":"5","key":"5409_CR27","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.ejps.2009.09.011","volume":"38","author":"F Barbato","year":"2009","unstructured":"Barbato F, Carpentiero C, Grumetto L, Rotonda MI. Enantioselective retention of beta-blocking agents on human serum albumin and alpha 1-acid glycoprotein HPLC columns: relationships with different scales of lipophilicity. Eur J Pharm Sci. 2009;38(5):472\u20138. https:\/\/doi.org\/10.1016\/j.ejps.2009.09.011.","journal-title":"Eur J Pharm Sci"},{"key":"5409_CR28","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.4155\/bio-2019-0074","volume":"11","author":"JP do Carmo","year":"2019","unstructured":"do Carmo JP, Phyo YZ, Palmeira A, Tiritan ME, Afonso C, Kijjoa A, Pinto MMM, Fernandes C. Enantioseparation, recognition mechanisms and binding of xanthones on human serum albumin by liquid chromatography. Bioanalysis. 2019;11:1255\u201374. https:\/\/doi.org\/10.4155\/bio-2019-0074.","journal-title":"Bioanalysis"},{"issue":"86","key":"5409_CR29","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.addr.2015.03.011","volume":"23","author":"G Lambrinidis","year":"2015","unstructured":"Lambrinidis G, Vallianatou T, Tsantili-Kakoulidou A. In vitro, in silico and integrated strategies for the estimation of plasma protein binding. A review Adv Drug Deliv Rev. 2015;23(86):27\u201345. https:\/\/doi.org\/10.1016\/j.addr.2015.03.011.","journal-title":"A review Adv Drug Deliv Rev"},{"key":"5409_CR30","doi-asserted-by":"publisher","first-page":"146","DOI":"10.2174\/157340911795677602","volume":"7","author":"X Meng","year":"2011","unstructured":"Meng X, Zhang H, Mezei M. Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput-Aided Drug Des. 2011;7:146\u201357. https:\/\/doi.org\/10.2174\/157340911795677602.","journal-title":"Curr Comput-Aided Drug Des"},{"key":"5409_CR31","doi-asserted-by":"publisher","unstructured":"He L, Wang Z, Wang Y, Liu X, Yang Y, Gao Y, Wang X, Liu B, Wang X (2016) Studies on the interaction between promethazine and human serum albumin in the presence of flavonoids by spectroscopic and molecular modeling techniques. Colloids Surf B: Biointerfaces. https:\/\/doi.org\/10.1016\/j.colsurfb.2016.06.001.","DOI":"10.1016\/j.colsurfb.2016.06.001"},{"key":"5409_CR32","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1002\/jps.2600660615","volume":"66","author":"J Judis","year":"1977","unstructured":"Judis J. Binding of codeine, morphine, and methadone to human serum proteins. J Pharm Sci. 1977;66:802\u20135.","journal-title":"J Pharm Sci"},{"key":"5409_CR33","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1002\/jps.2600690119","volume":"69","author":"J Judis","year":"1980","unstructured":"Judis J. Protein concentration effects on binding of 14c-codeine, i4c-morphine, and 3h-methadone to human serum albumin. J Pharm Sci. 1980;69:71\u20133. https:\/\/doi.org\/10.1002\/jps.2600690119.","journal-title":"J Pharm Sci"},{"key":"5409_CR34","first-page":"824","volume":"11","author":"G Sudlow","year":"1975","unstructured":"Sudlow G, Birkett DJ, Wade DN. The characterization of two specific drug binding sites on human serum albumin. Mol Pharmacol. 1975;11:824\u201332.","journal-title":"Mol Pharmacol"},{"key":"5409_CR35","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0378-4347(01)00482-0","volume":"768","author":"DS Hage","year":"2002","unstructured":"Hage DS. High-performance affinity chromatography: a powerful tool for studying serum protein binding. J Chromatogr B. 2002;768:3\u201330.","journal-title":"J Chromatogr B"},{"key":"5409_CR36","doi-asserted-by":"publisher","first-page":"313","DOI":"10.2174\/138920011795202938","volume":"12","author":"DS Hage","year":"2011","unstructured":"Hage DS, Anguizola J, Barnaby O, Jackson A, Yoo MJ, Papastavros E, Pfaunmiller E, Sobansky M, Tong Z. Characterization of drug interactions with serum proteins by using high-performance affinity chromatography. Curr Drug Metab. 2011;12:313\u201328. https:\/\/doi.org\/10.2174\/138920011795202938.","journal-title":"Curr Drug Metab"},{"key":"5409_CR37","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.jchromb.2014.01.007","volume":"968","author":"M Pistolozzi","year":"2014","unstructured":"Pistolozzi M, Fortugno C, Franchini C, Corbo F, Muraglia M, Roy M, F\u00e9lix G, Bertucci C. Species-dependent binding of tocainide analogues to albumin: Affinity chromatography and circular dichroism study. J Chromatogr B Biomed Appl. 2014;968:69\u201378. https:\/\/doi.org\/10.1016\/j.jchromb.2014.01.007.","journal-title":"J Chromatogr B Biomed Appl"},{"key":"5409_CR38","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.jchromb.2008.05.029","volume":"870","author":"HS Kim","year":"2008","unstructured":"Kim HS, Wainer IW. Rapid analysis of the interactions between drugs and human serum albumin (HSA) using high-performance affinity chromatography (HPAC). J Chromatogr B Analyt Technol Biomed Life Sci. 2008;870:22\u20136. https:\/\/doi.org\/10.1016\/j.jchromb.2008.05.029.","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"5409_CR39","doi-asserted-by":"publisher","unstructured":"Rose PW, Prli\u0107 A, Bi C, Bluhm WF, Christie CH, Dutta S, Green RK, Goodsell DS, Westbrook JD, Woo J, Young J, Zardecki C, Berman HM, Bourne PE, Burley SK (2015) The RCSB Protein Data Bank: views of structural biology for basic and applied research and education. Nucleic Acids Res. 43(D345-D356). https:\/\/doi.org\/10.1093\/nar\/gku1214.","DOI":"10.1093\/nar\/gku1214"},{"key":"5409_CR40","unstructured":"Hutchison GR, Morley C, James C, Swain C, De Winter H, Vandermeersch T, O\u2019Boyle NM. Open Babel Documentation. 2011;151."},{"key":"5409_CR41","unstructured":"Dennington RD, Keith TA, Millam JM. GaussView 5.0. Wallingford, US. 2008."},{"key":"5409_CR42","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J Comput Chem. 2010;31:455\u201361. https:\/\/doi.org\/10.1002\/jcc.21334.","journal-title":"J Comput Chem"},{"key":"5409_CR43","unstructured":"Schr\u00f6dinger LL. O sistema gr\u00e1fico molecular PyMOL. 1\u20138 edn. 2015."},{"key":"5409_CR44","doi-asserted-by":"publisher","unstructured":"Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules. Sci Rep. 7. https:\/\/doi.org\/10.1038\/srep42717.","DOI":"10.1038\/srep42717"},{"key":"5409_CR45","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.chroma.2004.08.010","volume":"1049","author":"HS Kim","year":"2004","unstructured":"Kim HS, Kye YS, Hage DS. Development and evaluation of N-hydroxysuccinimide-activated silica for immobilizing human serum albumin in liquid chromatography columns. J Chromatogr A. 2004;1049:51\u201361. https:\/\/doi.org\/10.1016\/j.chroma.2004.08.010.","journal-title":"J Chromatogr A"},{"key":"5409_CR46","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jpba.2005.12.002","volume":"42","author":"C Bertucci","year":"2006","unstructured":"Bertucci C, Cimitan S, Riva A, Morazzi P. Binding studies of taxanes to human serum albumin by bioaffinity chromatography and circular dichroism. J Pharm Biomed Anal. 2006;42:81\u20137. https:\/\/doi.org\/10.1016\/j.jpba.2005.12.002.","journal-title":"J Pharm Biomed Anal"},{"issue":"1","key":"5409_CR47","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jchromb.2008.05.022","volume":"875","author":"J Haginaka","year":"2008","unstructured":"Haginaka J. Recent progresses in protein-based chiral stationary phases for enantioseparations in liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;875(1):12\u20139. https:\/\/doi.org\/10.1016\/j.jchromb.2008.05.022.","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"5409_CR48","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1016\/j.jpba.2006.02.050","volume":"41","author":"H Chen","year":"2006","unstructured":"Chen H, Gong Z, Zhang Z. Coupling microdialysis with flow-injection chemiluminescence detection for a protein\u2013drug interaction study. J Pharm Biomed Anal. 2006;41:1412\u20137. https:\/\/doi.org\/10.1016\/j.jpba.2006.02.050.","journal-title":"J Pharm Biomed Anal"},{"key":"5409_CR49","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jmb.2005.07.075","volume":"353","author":"J Ghuman","year":"2005","unstructured":"Ghuman J, Zunszain PA, Petitpas I, Bhattacharya AA, Otagiri M, Curry SH. Structural basis of the drug-binding specificity of human serum albumin. J Mol Biol. 2005;353:38\u201352. https:\/\/doi.org\/10.1016\/j.jmb.2005.07.075.","journal-title":"J Mol Biol"},{"key":"5409_CR50","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1021\/jm7012826","volume":"51","author":"E L\u00e1zaro","year":"2008","unstructured":"L\u00e1zaro E, Lowe PJ, Birand X, Faller B. New approach to measure protein binding based on a parallel artificial membrane assay and human serum albumin. J Med Chem. 2008;51:2009\u201317. https:\/\/doi.org\/10.1021\/jm7012826.","journal-title":"J Med Chem"},{"key":"5409_CR51","doi-asserted-by":"publisher","unstructured":"More J, Bulmer M (2013) Human serum albumin: a multifunctional plasma protein. In: Wiley (ed) Production of Plasma Proteins for Therapeutic Use. pp 159\u2013183. https:\/\/doi.org\/10.1002\/9781118356807.ch12.","DOI":"10.1002\/9781118356807.ch12"},{"key":"5409_CR52","doi-asserted-by":"publisher","first-page":"48","DOI":"10.5599\/admet.1.4.24","volume":"1","author":"G V\u00f6lgyi","year":"2013","unstructured":"V\u00f6lgyi G, Marosi A, Tak\u00e1cs-Nov\u00e1k K, Avdeef A. Salt solubility products of diprenorphine hydrochloride, codeine and lidocaine hydrochlorides and phosphates \u2013 novel method of data analysis not dependent on explicit solubility equations. ADMET & DMPK. 2013;1:48\u201362. https:\/\/doi.org\/10.5599\/admet.1.4.24.","journal-title":"ADMET & DMPK"},{"key":"5409_CR53","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.3390\/molecules26071917","volume":"26","author":"BM EH-Haj","year":"2021","unstructured":"EH-Haj BM. Metabolic N-dealkylation and N-oxidation as elucidators of the role of alkylamino moieties in drugs acting at various receptors. Molecules. 2021;26:1917. https:\/\/doi.org\/10.3390\/molecules26071917.","journal-title":"Molecules"},{"key":"5409_CR54","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1097\/00008571-199610000-00009","volume":"16","author":"K Nakamura","year":"1996","unstructured":"Nakamura K, Yokoi T, Inoue K, Shimada N, Ohashi N, Kume T, Kamataki T. CYP2D6 is the principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes. Pharmacogenetics. 1996;16:449\u201357. https:\/\/doi.org\/10.1097\/00008571-199610000-00009.","journal-title":"Pharmacogenetics"},{"key":"5409_CR55","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1111\/j.1365-2125.1983.tb01501.x","volume":"15","author":"G Taylor","year":"1983","unstructured":"Taylor G, Houston JB, Shaffer J, Maweri G. Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man. Br J Clin Pharmacol. 1983;15:287\u201393. https:\/\/doi.org\/10.1111\/j.1365-2125.1983.tb01501.x.","journal-title":"Br J Clin Pharmacol"},{"key":"5409_CR56","doi-asserted-by":"publisher","unstructured":"Zhao X, Li Q, Chen J, Xiao C, Bian L, Zheng J, Zheng X, Li Z, Zhang Y (2014) Exploring drug\u2013protein interactions using the relationship between injection volume and capacity factor. J Chromatogr A. 137\u2013144. https:\/\/doi.org\/10.1016\/j.chroma.2014.03.017.","DOI":"10.1016\/j.chroma.2014.03.017"},{"issue":"2","key":"5409_CR57","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.jlumin.2010.10.014","volume":"131","author":"L He","year":"2011","unstructured":"He L, Wang X, Liu B, Wang J, Sun Y, Gao E, Xu S. Study on the interaction between promethazine hydrochloride and bovine serum albumin by fluorescence spectroscopy. J Lumin. 2011;131(2):285\u201390. https:\/\/doi.org\/10.1016\/j.jlumin.2010.10.014.","journal-title":"J Lumin"},{"issue":"6","key":"5409_CR58","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1002\/jps.2600820629","volume":"82","author":"TAG Noctor","year":"1993","unstructured":"Noctor TAG, Diaz-Perez MJ, Wainer IW. Use of a human serum albumin-based stationary phase for high-performance liquid chromatography as a tool for the rapid determination of drug-plasma protein binding. J Pharm Sci. 1993;82(6):675\u20136. https:\/\/doi.org\/10.1002\/jps.2600820629.","journal-title":"J Pharm Sci"},{"key":"5409_CR59","doi-asserted-by":"publisher","first-page":"3056","DOI":"10.1002\/elps.200700222","volume":"28","author":"MA Mart\u00ednez-G\u00f3mez","year":"2007","unstructured":"Mart\u00ednez-G\u00f3mez MA, Villanueva-Cama\u00f1as RM, Sagrado S, Medina-Hern\u00e1ndez MJ. Evaluation of enantioselective binding of basic drugs to plasma by ACE. J Electrophor. 2007;28:3056\u201363. https:\/\/doi.org\/10.1002\/elps.200700222.","journal-title":"J Electrophor"},{"key":"5409_CR60","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/S0003-2670(99)00248-2","volume":"392","author":"XX Zhang","year":"1999","unstructured":"Zhang XX, Hong F, Chang L. Enantiomeric separation of promethazine and D, L-a-amino-b-[4-(1,2dihydro-2-oxo-quinoline)] propionic acid drugs by capillary zone electrophoresis using albumin as chiral selectors. Anal Chim Acta. 1999;392:175\u201381. https:\/\/doi.org\/10.1016\/S0003-2670(99)00248-2.","journal-title":"Anal Chim Acta"},{"key":"5409_CR61","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/B978-0-12-814423-7.00011-3","volume-title":"Dosage form design considerations","author":"PK Deb","year":"2018","unstructured":"Deb PK, Al-Attraqchi O, Prasad MR, Tekade RK. Protein and tissue binding: implication on pharmacokinetic parameters. In: Tekade RK, editor. Dosage form design considerations, vol. i. Advances in Pharmaceutical Product Development and Research: Academic Press; 2018. p. 371\u201399."},{"key":"5409_CR62","doi-asserted-by":"publisher","first-page":"36267","DOI":"10.1039\/c4ra04630g","volume":"4","author":"AS Sharma","year":"2014","unstructured":"Sharma AS, Anandakumar S, Ilanchelian M. In vitro investigation of domain specific interactions of phenothiazine dye with serum proteins by spectroscopic and molecular docking approaches. RSC Adv. 2014;4:36267\u201381. https:\/\/doi.org\/10.1039\/c4ra04630g.","journal-title":"RSC Adv"},{"key":"5409_CR63","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.ejps.2012.01.007","volume":"45","author":"DI P\u00e9rez","year":"2012","unstructured":"P\u00e9rez DI, Pistolozzi M, Palomo V, Redondo M, Fortugno C, Gil C, Felix G, Martinez A, Bertucci C. 5-Imino-1,2\u20134-thiadiazoles and quinazolines derivatives as glycogen synthase kinase 3b (GSK-3b) and phosphodiesterase 7 (PDE7) inhibitors: Determination of blood\u2013brain barrier penetration and binding to human serum albumin. Eur J Pharm Sci. 2012;45:677\u201384. https:\/\/doi.org\/10.1016\/j.ejps.2012.01.007.","journal-title":"Eur J Pharm Sci"},{"key":"5409_CR64","doi-asserted-by":"publisher","unstructured":"Bai G, Pan Y, Zhang Y, Li Y, Wang J, Wang Y, Teng W, Jin G, Geng F, Cao J (2023) Research advances of molecular docking and molecular dynamic simulation in recognizing interaction between muscle proteins and exogenous additives. Food Chem. 429. https:\/\/doi.org\/10.1016\/j.foodchem.2023.136836.","DOI":"10.1016\/j.foodchem.2023.136836"},{"key":"5409_CR65","doi-asserted-by":"publisher","first-page":"932","DOI":"10.6026\/97320630017932","volume":"17","author":"SM Patil","year":"2021","unstructured":"Patil SM, Maruthi KR, Bajpe SN, Vyshali VM, Sushmitha S, Akhila C, Ramu R. Comparative molecular docking and simulation analysis of molnupiravir and remdesivir with SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Bioinformation. 2021;17:932\u20139. https:\/\/doi.org\/10.6026\/97320630017932.","journal-title":"Bioinformation"},{"key":"5409_CR66","doi-asserted-by":"publisher","first-page":"323","DOI":"10.2174\/1381612053382106","volume":"11","author":"V Mohan","year":"2005","unstructured":"Mohan V, Gibbs AC, Cummings MD, Jaeger EP, DesJarlais RL. Docking: successes and challenges. Curr Pharm Des. 2005;11:323\u201333. https:\/\/doi.org\/10.2174\/1381612053382106.","journal-title":"Curr Pharm Des"},{"key":"5409_CR67","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1021\/jm0302997","volume":"47","author":"M Kontoyianni","year":"2004","unstructured":"Kontoyianni M, McClellan LM, Sokol GS. Evaluation of docking performance: comparative data on docking algorithms. J Med Chem. 2004;47:558\u201365. https:\/\/doi.org\/10.1021\/jm0302997.","journal-title":"J Med Chem"}],"container-title":["Analytical and Bioanalytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00216-024-05409-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00216-024-05409-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00216-024-05409-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T09:07:22Z","timestamp":1722503242000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00216-024-05409-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,4]]},"references-count":67,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["5409"],"URL":"https:\/\/doi.org\/10.1007\/s00216-024-05409-3","relation":{},"ISSN":["1618-2642","1618-2650"],"issn-type":[{"value":"1618-2642","type":"print"},{"value":"1618-2650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,4]]},"assertion":[{"value":"1 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}