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A newly developed and fully validated HPLC method for simultenous determination of in-situ single pass intestinal permeability of domperidone, metoprolol tartarate and phenol red

Yıl 2023, Cilt: 27 Sayı: 3, 967 - 979, 28.06.2025

Saniye Özcan , Emre Şefik Çağlar , Mustafa Sinan Kaynak , Neslihan Üstündağ

Öz

One of the most popular methods for figuring out a drug’s intestinal permeability is the intestinal perfusion (SPIP) approach. Metoprolol as tartrate and phenol red are frequently utilized as reference compounds in perfusion tests to assess the permeability coefficient of the study’s focus component, Domperidone maleate. Our study’s goal was to create and validate a reversed-phase liquid chromatographic technique for the simultaneous detection of Domperidone maleate, metoprolol, and phenol red for use in intestinal perfusion studies. The analysis was performed on a C18 column 150 × 1.5 mm, 5.0 μm using a mobile phase consisting of methanol: 20 mM potassium dihydrogen phosphate buffer 43:57, v/v; pH 3.1. The procedure was validated using the FDA’s standards for stability, linearity, precision, and accuracy. All calibration curves were linear r2> 0.99. The system suitability parameters of the method are the required limits all analytes. The in situ intestinal permeability experiments can easily be standardized with the help of this newly created and proven approach.

Anahtar Kelimeler

Domperidone HPLC validation Metoprolol tartarate Phenol Red

Kaynakça

  • [1.] Dahan A, Miller JM, Amidon GL. Prediction of solubility and permeability class membership: provisional BCS classification of the world's top oral drugs. AAPS J. 2009;11(4):740-6. http://dx.doi.org/10.1208/s12248-009-9144-x.
  • [2.] Lennernas H. Intestinal permeability and its relevance for absorption and elimination. Xenobiotica. 2007;37(10-11):1015-51. http://dx.doi.org/10.1080/00498250701704819.
  • [3.] Lozoya-Agullo I, Zur M, Wolk O, Beig A, Gonzalez-Alvarez I, Gonzalez-Alvarez M, et al. In-situ intestinal rat perfusions for human Fabs prediction and BCS permeability class determination: Investigation of the single-pass vs. the Doluisio experimental approaches. Int J Pharm. 2015;480(1-2):1-7. http://dx.doi.org/10.1016/j.ijpharm.2015.01.014.
  • [4.] Doluisio JT, Tan GH, Billups NF, Diamond L. Drug absorption. II. Effect of fasting on intestinal drug absorption. J Pharm Sci. 1969;58(10):1200-2. http://dx.doi.org/10.1002/jps.2600581007.
  • [5.] Amidon GL, Sinko PJ, Fleisher D. Estimating human oral fraction dose absorbed: a correlation using rat intestinal membrane permeability for passive and carrier-mediated compounds. Pharm Res. 1988;5(10):651-4. http://dx.doi.org/10.1023/a:1015927004752.
  • [6.] Lozoya-Agullo I, Gonzalez-Alvarez I, Zur M, Fine-Shamir N, Cohen Y, Markovic M, et al. Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat-Biophysical Model and Predictions Based on Caco-2. Pharm. Res. 2018;35(1):1-23. http://dx.doi.org/10.1007/s11095-017-2331-z.
  • [7.] Reddymasu SC, Soykan I, McCallum RW. Domperidone: review of pharmacology and clinical applications in gastroenterology. Am J Gastroenterol. 2007;102(9):2036-45. http://dx.doi.org/10.1111/j.1572-0241.2007.01255.x.
  • [8.] Breuil L, Goutal S, Marie S, Del Vecchio A, Audisio D, Soyer A, et al. Comparison of the Blood-Brain Barrier Transport and Vulnerability to P-Glycoprotein-Mediated Drug-Drug Interaction of Domperidone versus Metoclopramide Assessed Using In Vitro Assay and PET Imaging. Pharmaceutics. 2022;14(8):1658. http://dx.doi.org/10.3390/pharmaceutics14081658.
  • [9.] Schey R, Saadi M, Midani D, Roberts AC, Parupalli R, Parkman HP. Domperidone to Treat Symptoms of Gastroparesis: Benefits and Side Effects from a Large Single-Center Cohort. Dig Dis Sci. 2016;61(12):3545-51. http://dx.doi.org/10.1007/s10620-016-4272-5.
  • [10.] Abbas G, Saadullah M, Rasul A, Shah S, Khan SM, Hanif M, et al. Development and validation of high-performance liquid chromatography method for the simultaneous monitoring of pantoprazole sodium sesquihydrate and domperidone maleate in plasma and its application to pharmacokinetic study. Acta Chromatogr. 2020;32(3):157-65. https://doi.org/10.1556/1326.2019.00525.
  • [11.] Afzal M, Muddassir M, Alarifi A, Ansari MT. Box-Behnken assisted validation and optimization of an RP-HPLC method for simultaneous determination of domperidone and lansoprazole. Separations. 2021;8(1):5. http://dx.doi.org/10.3390/separations8010005.
  • [12.] Sultan MA, Maher HM, Alzoman NZ, Alshehri MM, Rizk MS, Elshahed MS, et al. Capillary electrophoretic determination of antimigraine formulations containing caffeine, ergotamine, paracetamol and domperidone or metoclopramide. J Chromatogr Sci. 2013;51(6):502-10. http://dx.doi.org/10.1093/chromsci/bms175.
  • [13.] Bhaskar KL, Lakshmi D, Sumalatha G, Suji G, Kumar K. Q-analysis and simultaneous equation method for estimation of domperidone and naproxen by UV spectrophotometry in bulk and tablet dosage form. Res J Pharm Technol. 2020;13(12):6050-4. http://dx.doi.org/10.5958/0974-360X.2020.01054.9.
  • [14.] Abdul MIM, Siddique S, Rahman SAU, Lateef D, Dan S, Bose A. Simple bioanalytical method development and validation of micronised domperidone 20 mg tablets using LCMS-MS and its pharmacokinetic application in healthy Indian volunteers. AJPP. 2018;12(27):416-20. http://dx.doi.org/https://doi.org/10.5897/AJPP2018.4955.
  • [15.] Wang X, Qin F, Jing L, Zhu Q, Li F, Xiong Z. Development and validation of UPLC-MS/MS method for determination of domperidone in human plasma and its pharmacokinetic application. Biomed Chromatogr. 2013;27(3):371-6. http://dx.doi.org/10.1002/bmc.2801.
  • [16.] Youssef AS, Argikar UA, Pathikonda M, Parkman HP, Nagar S. Identification of domperidone metabolites in plasma and urine of gastroparesis patients with LC-ESI-MS/MS. Xenobiotica. 2013;43(12):1073-83. http://dx.doi.org/10.3109/00498254.2013.797623.
  • [17.] Araujo P. Key aspects of analytical method validation and linearity evaluation. J. Chromatogr. B. 2009;877(23):2224-34. https://doi.org/10.1016/j.jchromb.2008.09.030.
  • [18.] Barton CA, Johnson NB, Mah ND, Beauchamp G, Hendrickson R. Successful treatment of a massive metoprolol overdose using intravenous lipid emulsion and hyperinsulinemia/euglycemia therapy. Pharmacotherapy. 2015;35(5):e56-60. http://dx.doi.org/10.1002/phar.1579.
  • [19.] Rathore R, Jain JP, Srivastava A, Jachak SM, Kumar N. Simultaneous determination of hydrazinocurcumin and phenol red in samples from rat intestinal permeability studies: HPLC method development and validation. J Pharm Biomed Anal. 2008;46(2):374-80. http://dx.doi.org/10.1016/j.jpba.2007.09.019.
  • [20.] Templeton I, Ravenstijn P, Sensenhauser C, Snoeys J. A physiologically based pharmacokinetic modeling approach to predict drug-drug interactions between domperidone and inhibitors of CYP3A4. Biopharm Drug Dispos. 2016;37(1):15-27. http://dx.doi.org/10.1002/bdd.1992.
  • [21.] Gulsun T, Sahin S. Development and Validation of a RP-HPLC Method for Simultaneous Determination of Metformin Hydrochloride, Phenol Red and Metoprolol Tartrate for Intestinal Perfusion Studies. Lat. Am. J. Pharm. 2016;35(1):50-7.
  • [22.] Kaynak MS, Buyuktuncel E, Caglar H, Sahin S. Determination of Regional Intestinal Permeability of Diclofenac and Metoprolol Using a Newly-Developed and Validated High Performance Liquid Chromatographic Method. Trop J Pharm Res. 2015;14(1):163-70. http://dx.doi.org/10.4314/tjpr.v14i1.23.
  • [23.] Dahlgren D, Lennernas H. Intestinal Permeability and Drug Absorption: Predictive Experimental, Computational and In Vivo Approaches. Pharmaceutics. 2019;11(8):411. http://dx.doi.org/10.3390/pharmaceutics11080411.
  • [24.] Incecayir T, Tsume Y, Amidon GL. Comparison of the permeability of metoprolol and labetalol in rat, mouse, and Caco-2 cells: use as a reference standard for BCS classification. Mol. Pharm. 2013;10(3):958-66.
  • [25.] Nagare N, Damre A, Singh KS, Mallurwar SR, Iyer S, Naik A, et al. Determination of site of absorption of propranolol in rat gut using in situ single-pass intestinal perfusion. Indian J Pharm Sci. 2010;72(5):625-9. http://dx.doi.org/10.4103/0250-474X.78533.
  • [26.] Ates M, Kaynak MS, Sahin S. Effect of permeability enhancers on paracellular permeability of acyclovir. J Pharm Pharmacol. 2016;68(6):781-90. http://dx.doi.org/10.1111/jphp.12551.
  • [27.] Ates M, Kaynak MS, Sahin S. Simultaneous Determination of Acyclovir Metoprolol and Phenol Red by a RP HPLC Method for Intestinal Perfusion Studies. Hacet. Univ. J. Fac. Pharm. 2015;35(2):146-61.
  • [28.] Gokce EH, Kaynak MS, Yurdasiper A, Ustundag-Okur N, Sahin S. Comparison of intestinal permeability of nebivolol hydrochloride loaded solid lipid nanoparticles with commercial nebivolol tablet. J Res Pharm. 2018;22(4):578-86. http://dx.doi.org/10.12991/jrp.2018.100.
  • [29.] Kaynak MS, Celebier M, Akgeyik E, Sahin S, Altinoz S. Application of HPLC to Investigate the Physicochemical Properties and Intestinal Permeability of Ketoprofen. Curr Pharm Anal. 2017;13(1):72-9. http://dx.doi.org/10.2174/1573412912666160422151409.
  • [30.] Kim JY, Ku YS. Enhanced absorption of indomethacin after oral or rectal administration of a self-emulsifying system containing indomethacin to rats. Int J Pharm. 2000;194(1):81-9. http://dx.doi.org/10.1016/s0378-5173(99)00367-1.
  • [31.] Mansia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 ESH-ESC Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Press. 2007;16(3):135-232. http://dx.doi.org/10.1080/08037050701461084.
  • [32.] Zhang Z, Gao F, Bu H, Xiao J, Li Y. Solid lipid nanoparticles loading candesartan cilexetil enhance oral bioavailability: in vitro characteristics and absorption mechanism in rats. Nanomedicine. 2012;8(5):740-7. http://dx.doi.org/10.1016/j.nano.2011.08.016.
  • [33.] Li H, Zhao X, Ma Y, Zhai G, Li L, Lou H. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J Control Release. 2009;133(3):238-44. http://dx.doi.org/10.1016/j.jconrel.2008.10.002.
  • [34.] Kheradmandnia S, Vasheghani-Farahani E, Nosrati M, Atyabi F. Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax. Nanomedicine-Nanotechnology Biology and Medicine. 2010;6(6):753-9. http://dx.doi.org/10.1016/j.nano.2010.06.003.
  • [35.] Fagerholm U, Johansson M, Lennernas H. Comparison between permeability coefficients in rat and human jejunum. Pharm. Res. 1996;13(9):1336-42. http://dx.doi.org/Doi 10.1023/A:1016065715308.

Yıl 2023, Cilt: 27 Sayı: 3, 967 - 979, 28.06.2025

Saniye Özcan , Emre Şefik Çağlar , Mustafa Sinan Kaynak , Neslihan Üstündağ

Öz

Kaynakça

  • [1.] Dahan A, Miller JM, Amidon GL. Prediction of solubility and permeability class membership: provisional BCS classification of the world's top oral drugs. AAPS J. 2009;11(4):740-6. http://dx.doi.org/10.1208/s12248-009-9144-x.
  • [2.] Lennernas H. Intestinal permeability and its relevance for absorption and elimination. Xenobiotica. 2007;37(10-11):1015-51. http://dx.doi.org/10.1080/00498250701704819.
  • [3.] Lozoya-Agullo I, Zur M, Wolk O, Beig A, Gonzalez-Alvarez I, Gonzalez-Alvarez M, et al. In-situ intestinal rat perfusions for human Fabs prediction and BCS permeability class determination: Investigation of the single-pass vs. the Doluisio experimental approaches. Int J Pharm. 2015;480(1-2):1-7. http://dx.doi.org/10.1016/j.ijpharm.2015.01.014.
  • [4.] Doluisio JT, Tan GH, Billups NF, Diamond L. Drug absorption. II. Effect of fasting on intestinal drug absorption. J Pharm Sci. 1969;58(10):1200-2. http://dx.doi.org/10.1002/jps.2600581007.
  • [5.] Amidon GL, Sinko PJ, Fleisher D. Estimating human oral fraction dose absorbed: a correlation using rat intestinal membrane permeability for passive and carrier-mediated compounds. Pharm Res. 1988;5(10):651-4. http://dx.doi.org/10.1023/a:1015927004752.
  • [6.] Lozoya-Agullo I, Gonzalez-Alvarez I, Zur M, Fine-Shamir N, Cohen Y, Markovic M, et al. Closed-Loop Doluisio (Colon, Small Intestine) and Single-Pass Intestinal Perfusion (Colon, Jejunum) in Rat-Biophysical Model and Predictions Based on Caco-2. Pharm. Res. 2018;35(1):1-23. http://dx.doi.org/10.1007/s11095-017-2331-z.
  • [7.] Reddymasu SC, Soykan I, McCallum RW. Domperidone: review of pharmacology and clinical applications in gastroenterology. Am J Gastroenterol. 2007;102(9):2036-45. http://dx.doi.org/10.1111/j.1572-0241.2007.01255.x.
  • [8.] Breuil L, Goutal S, Marie S, Del Vecchio A, Audisio D, Soyer A, et al. Comparison of the Blood-Brain Barrier Transport and Vulnerability to P-Glycoprotein-Mediated Drug-Drug Interaction of Domperidone versus Metoclopramide Assessed Using In Vitro Assay and PET Imaging. Pharmaceutics. 2022;14(8):1658. http://dx.doi.org/10.3390/pharmaceutics14081658.
  • [9.] Schey R, Saadi M, Midani D, Roberts AC, Parupalli R, Parkman HP. Domperidone to Treat Symptoms of Gastroparesis: Benefits and Side Effects from a Large Single-Center Cohort. Dig Dis Sci. 2016;61(12):3545-51. http://dx.doi.org/10.1007/s10620-016-4272-5.
  • [10.] Abbas G, Saadullah M, Rasul A, Shah S, Khan SM, Hanif M, et al. Development and validation of high-performance liquid chromatography method for the simultaneous monitoring of pantoprazole sodium sesquihydrate and domperidone maleate in plasma and its application to pharmacokinetic study. Acta Chromatogr. 2020;32(3):157-65. https://doi.org/10.1556/1326.2019.00525.
  • [11.] Afzal M, Muddassir M, Alarifi A, Ansari MT. Box-Behnken assisted validation and optimization of an RP-HPLC method for simultaneous determination of domperidone and lansoprazole. Separations. 2021;8(1):5. http://dx.doi.org/10.3390/separations8010005.
  • [12.] Sultan MA, Maher HM, Alzoman NZ, Alshehri MM, Rizk MS, Elshahed MS, et al. Capillary electrophoretic determination of antimigraine formulations containing caffeine, ergotamine, paracetamol and domperidone or metoclopramide. J Chromatogr Sci. 2013;51(6):502-10. http://dx.doi.org/10.1093/chromsci/bms175.
  • [13.] Bhaskar KL, Lakshmi D, Sumalatha G, Suji G, Kumar K. Q-analysis and simultaneous equation method for estimation of domperidone and naproxen by UV spectrophotometry in bulk and tablet dosage form. Res J Pharm Technol. 2020;13(12):6050-4. http://dx.doi.org/10.5958/0974-360X.2020.01054.9.
  • [14.] Abdul MIM, Siddique S, Rahman SAU, Lateef D, Dan S, Bose A. Simple bioanalytical method development and validation of micronised domperidone 20 mg tablets using LCMS-MS and its pharmacokinetic application in healthy Indian volunteers. AJPP. 2018;12(27):416-20. http://dx.doi.org/https://doi.org/10.5897/AJPP2018.4955.
  • [15.] Wang X, Qin F, Jing L, Zhu Q, Li F, Xiong Z. Development and validation of UPLC-MS/MS method for determination of domperidone in human plasma and its pharmacokinetic application. Biomed Chromatogr. 2013;27(3):371-6. http://dx.doi.org/10.1002/bmc.2801.
  • [16.] Youssef AS, Argikar UA, Pathikonda M, Parkman HP, Nagar S. Identification of domperidone metabolites in plasma and urine of gastroparesis patients with LC-ESI-MS/MS. Xenobiotica. 2013;43(12):1073-83. http://dx.doi.org/10.3109/00498254.2013.797623.
  • [17.] Araujo P. Key aspects of analytical method validation and linearity evaluation. J. Chromatogr. B. 2009;877(23):2224-34. https://doi.org/10.1016/j.jchromb.2008.09.030.
  • [18.] Barton CA, Johnson NB, Mah ND, Beauchamp G, Hendrickson R. Successful treatment of a massive metoprolol overdose using intravenous lipid emulsion and hyperinsulinemia/euglycemia therapy. Pharmacotherapy. 2015;35(5):e56-60. http://dx.doi.org/10.1002/phar.1579.
  • [19.] Rathore R, Jain JP, Srivastava A, Jachak SM, Kumar N. Simultaneous determination of hydrazinocurcumin and phenol red in samples from rat intestinal permeability studies: HPLC method development and validation. J Pharm Biomed Anal. 2008;46(2):374-80. http://dx.doi.org/10.1016/j.jpba.2007.09.019.
  • [20.] Templeton I, Ravenstijn P, Sensenhauser C, Snoeys J. A physiologically based pharmacokinetic modeling approach to predict drug-drug interactions between domperidone and inhibitors of CYP3A4. Biopharm Drug Dispos. 2016;37(1):15-27. http://dx.doi.org/10.1002/bdd.1992.
  • [21.] Gulsun T, Sahin S. Development and Validation of a RP-HPLC Method for Simultaneous Determination of Metformin Hydrochloride, Phenol Red and Metoprolol Tartrate for Intestinal Perfusion Studies. Lat. Am. J. Pharm. 2016;35(1):50-7.
  • [22.] Kaynak MS, Buyuktuncel E, Caglar H, Sahin S. Determination of Regional Intestinal Permeability of Diclofenac and Metoprolol Using a Newly-Developed and Validated High Performance Liquid Chromatographic Method. Trop J Pharm Res. 2015;14(1):163-70. http://dx.doi.org/10.4314/tjpr.v14i1.23.
  • [23.] Dahlgren D, Lennernas H. Intestinal Permeability and Drug Absorption: Predictive Experimental, Computational and In Vivo Approaches. Pharmaceutics. 2019;11(8):411. http://dx.doi.org/10.3390/pharmaceutics11080411.
  • [24.] Incecayir T, Tsume Y, Amidon GL. Comparison of the permeability of metoprolol and labetalol in rat, mouse, and Caco-2 cells: use as a reference standard for BCS classification. Mol. Pharm. 2013;10(3):958-66.
  • [25.] Nagare N, Damre A, Singh KS, Mallurwar SR, Iyer S, Naik A, et al. Determination of site of absorption of propranolol in rat gut using in situ single-pass intestinal perfusion. Indian J Pharm Sci. 2010;72(5):625-9. http://dx.doi.org/10.4103/0250-474X.78533.
  • [26.] Ates M, Kaynak MS, Sahin S. Effect of permeability enhancers on paracellular permeability of acyclovir. J Pharm Pharmacol. 2016;68(6):781-90. http://dx.doi.org/10.1111/jphp.12551.
  • [27.] Ates M, Kaynak MS, Sahin S. Simultaneous Determination of Acyclovir Metoprolol and Phenol Red by a RP HPLC Method for Intestinal Perfusion Studies. Hacet. Univ. J. Fac. Pharm. 2015;35(2):146-61.
  • [28.] Gokce EH, Kaynak MS, Yurdasiper A, Ustundag-Okur N, Sahin S. Comparison of intestinal permeability of nebivolol hydrochloride loaded solid lipid nanoparticles with commercial nebivolol tablet. J Res Pharm. 2018;22(4):578-86. http://dx.doi.org/10.12991/jrp.2018.100.
  • [29.] Kaynak MS, Celebier M, Akgeyik E, Sahin S, Altinoz S. Application of HPLC to Investigate the Physicochemical Properties and Intestinal Permeability of Ketoprofen. Curr Pharm Anal. 2017;13(1):72-9. http://dx.doi.org/10.2174/1573412912666160422151409.
  • [30.] Kim JY, Ku YS. Enhanced absorption of indomethacin after oral or rectal administration of a self-emulsifying system containing indomethacin to rats. Int J Pharm. 2000;194(1):81-9. http://dx.doi.org/10.1016/s0378-5173(99)00367-1.
  • [31.] Mansia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 ESH-ESC Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Press. 2007;16(3):135-232. http://dx.doi.org/10.1080/08037050701461084.
  • [32.] Zhang Z, Gao F, Bu H, Xiao J, Li Y. Solid lipid nanoparticles loading candesartan cilexetil enhance oral bioavailability: in vitro characteristics and absorption mechanism in rats. Nanomedicine. 2012;8(5):740-7. http://dx.doi.org/10.1016/j.nano.2011.08.016.
  • [33.] Li H, Zhao X, Ma Y, Zhai G, Li L, Lou H. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J Control Release. 2009;133(3):238-44. http://dx.doi.org/10.1016/j.jconrel.2008.10.002.
  • [34.] Kheradmandnia S, Vasheghani-Farahani E, Nosrati M, Atyabi F. Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax. Nanomedicine-Nanotechnology Biology and Medicine. 2010;6(6):753-9. http://dx.doi.org/10.1016/j.nano.2010.06.003.
  • [35.] Fagerholm U, Johansson M, Lennernas H. Comparison between permeability coefficients in rat and human jejunum. Pharm. Res. 1996;13(9):1336-42. http://dx.doi.org/Doi 10.1023/A:1016065715308.
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılıkta Analitik Kimya
Bölüm Articles
Yazarlar

Saniye Özcan 0000-0002-5492-0457

Emre Şefik Çağlar 0000-0003-2010-4918

Mustafa Sinan Kaynak 0000-0003-2917-2407

Neslihan Üstündağ 0000-0002-3210-3747

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2023 Cilt: 27 Sayı: 3

Kaynak Göster

APA Özcan, S., Çağlar, E. Ş., Kaynak, M. S., Üstündağ, N. (2025). A newly developed and fully validated HPLC method for simultenous determination of in-situ single pass intestinal permeability of domperidone, metoprolol tartarate and phenol red. Journal of Research in Pharmacy, 27(3), 967-979.
AMA Özcan S, Çağlar EŞ, Kaynak MS, Üstündağ N. A newly developed and fully validated HPLC method for simultenous determination of in-situ single pass intestinal permeability of domperidone, metoprolol tartarate and phenol red. J. Res. Pharm. Haziran 2025;27(3):967-979.
Chicago Özcan, Saniye, Emre Şefik Çağlar, Mustafa Sinan Kaynak, ve Neslihan Üstündağ. “A Newly Developed and Fully Validated HPLC Method for Simultenous Determination of in-Situ Single Pass Intestinal Permeability of Domperidone, Metoprolol Tartarate and Phenol Red”. Journal of Research in Pharmacy 27, sy. 3 (Haziran 2025): 967-79.
EndNote Özcan S, Çağlar EŞ, Kaynak MS, Üstündağ N (01 Haziran 2025) A newly developed and fully validated HPLC method for simultenous determination of in-situ single pass intestinal permeability of domperidone, metoprolol tartarate and phenol red. Journal of Research in Pharmacy 27 3 967–979.
IEEE S. Özcan, E. Ş. Çağlar, M. S. Kaynak, ve N. Üstündağ, “A newly developed and fully validated HPLC method for simultenous determination of in-situ single pass intestinal permeability of domperidone, metoprolol tartarate and phenol red”, J. Res. Pharm., c. 27, sy. 3, ss. 967–979, 2025.
ISNAD Özcan, Saniye vd. “A Newly Developed and Fully Validated HPLC Method for Simultenous Determination of in-Situ Single Pass Intestinal Permeability of Domperidone, Metoprolol Tartarate and Phenol Red”. Journal of Research in Pharmacy 27/3 (Haziran 2025), 967-979.
JAMA Özcan S, Çağlar EŞ, Kaynak MS, Üstündağ N. A newly developed and fully validated HPLC method for simultenous determination of in-situ single pass intestinal permeability of domperidone, metoprolol tartarate and phenol red. J. Res. Pharm. 2025;27:967–979.
MLA Özcan, Saniye vd. “A Newly Developed and Fully Validated HPLC Method for Simultenous Determination of in-Situ Single Pass Intestinal Permeability of Domperidone, Metoprolol Tartarate and Phenol Red”. Journal of Research in Pharmacy, c. 27, sy. 3, 2025, ss. 967-79.
Vancouver Özcan S, Çağlar EŞ, Kaynak MS, Üstündağ N. A newly developed and fully validated HPLC method for simultenous determination of in-situ single pass intestinal permeability of domperidone, metoprolol tartarate and phenol red. J. Res. Pharm. 2025;27(3):967-79.