Abstract
Background: A high-performance liquid chromatography (HPLC) method was developed for the determination of Pantoprazole Sodium (PPZ) in the presence of its degradation products. The degradation of PPZ was studied in simulated intestinal fluid (SIF) and simulated gastric fluids (SGF) in various temperature conditions.
Aim: This study aimed to establish a simple, sensitive, and rapid RP HPLC method for in-vitro determination of Pantoprazole Sodium and its degradation products in simulated gastric and intestinal fluids.
Objective: Pantoprazole is acid labile drug. In order to determine pantoprazole in various oral dosage forms, the stability-indicating assay of PPZ was performed in phosphate buffer (pH 6.8) representing simulated intestinal fluid (SIF) and in 0.1 molars (M) Hydrochloric acid (HCl) as simulated gastric fluid (SGF) at two different temperature conditions, i.e., 25°C and 0°C, respectively.
Methods: Pantoprazole sodium was obtained from the Akums laboratory in Haridwar. The analysis was performed by high-performance liquid chromatography (HPLC), Shimadzu, equipped with two LC-10 AD VP solvent-delivery modules, a SPD-10A UV–-visible detector, and a manual injector valve with 20 μL sample loop. Phenomenex ODS analytical column (150 mm × 4.6 mm i.d., 5 μm particles) was done under reversed-phase partition chromatographic conditions. The mobile phase was phosphate buffer and acetonitrile (ACN) of pH 7.4, respectively, optimized in a 70:30 (v/v) ratio followed by filtration through a 0.45 μm membrane filter and degassed by ultrasonicator before use. The mobile phase was delivered at the flow rate of 2 mL/min. The various parameters, such as linearity, accuracy and precision of the analytical method, were studied.
Results: The standard curve of PPZ was linear (R2>0.99) over the concentration range of 5-30 μg/mL, and the relative standard deviation (RSD) values for intra-day and inter-day variations were in the range of 1.0-1.8%. The range of RSD was within ±2.
Conclusion: The stability of PPZ in aqueous solution was pH dependent. The rate of degradation increases with decreasing pH. The pH stability of pantoprazole was studied at the above-mentioned temperature conditions. The PPZ peaks were analyzed by comparing them with fresh samples and were stable in SIF solution after 24 hours elapsed time at pH 6.8. The obtained degraded peaks in SGF (pH 1) were successfully separated from the PPZ.
Graphical Abstract
[1]
Avner, D.L. Clinical experience with pantoprazole in gastroesophageal reflux disease. Clin. Ther., 2000, 22(10), 1169-1185.
[http://dx.doi.org/10.1016/S0149-2918(00)83061-1]
[http://dx.doi.org/10.1016/S0149-2918(00)83061-1]
[2]
Beil, W.; Staar, U.; Sewing, K.F. Pantoprazole: a novel H+/K+-ATPase inhibitor with an improved pH stability. Eur. J. Pharmacol., 1992, 218(2-3), 265-271.
[http://dx.doi.org/10.1016/0014-2999(92)90178-7] [PMID: 1330598]
[http://dx.doi.org/10.1016/0014-2999(92)90178-7] [PMID: 1330598]
[3]
Bharathi, D.V.; Hotha, K.K.; Jagadeesh, B.; Chatki, P.K.; Thriveni, K.; Mullangi, R.; Naidu, A. Simultaneous estimation of four proton pump inhibitors—lansoprazole, omeprazole, pantoprazole and rabeprazole: development of a novel generic HPLC‐UV method and its application to clinical pharmacokinetic study. Biomed. Chromatogr., 2009, 23(7), 732-739.
[http://dx.doi.org/10.1002/bmc.1177] [PMID: 19360758]
[http://dx.doi.org/10.1002/bmc.1177] [PMID: 19360758]
[4]
Gupta, H.P.; Saini, K.; Dhingra, P.; Pandey, R. Study of acid catalyzed reactions of proton pump inhibitors at D.M.E. Port. Electrochem. Acta, 2007, 26(5), 433-448.
[http://dx.doi.org/10.4152/pea.200805433]
[http://dx.doi.org/10.4152/pea.200805433]
[5]
National Library of Medicine. Pantoprazole Sodium., 2004. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Pantoprazole-Sodium(Cited 2023 Oct. 12).
[6]
Jung, S.W.; Kim, S.Y.; Choe, J.W.; Hyun, J.J.; Jung, Y.K.; Koo, J.S.; Yim, H.J.; Lee, S.W. Standard and double‐dose intravenous proton pump inhibitor injections for prevention of bleeding after endoscopic resection. J. Gastroenterol. Hepatol., 2017, 32(4), 778-781.
[http://dx.doi.org/10.1111/jgh.13597] [PMID: 27637734]
[http://dx.doi.org/10.1111/jgh.13597] [PMID: 27637734]
[7]
Kherad, O.; Restellini, S.; Martel, M.; Barkun, A. Proton pump inhibitors for upper gastrointestinal bleeding. Best Pract. Res. Clin. Gastroenterol., 2019, 42-43, 101609.
[http://dx.doi.org/10.1016/j.bpg.2019.04.002] [PMID: 31785730]
[http://dx.doi.org/10.1016/j.bpg.2019.04.002] [PMID: 31785730]
[8]
Gupta, A.; Akhtar, J.; Rastogi, K.C.; Badruddeen,; Khan, M.I.; Ahmad, M. Oral disintegrating tablets of proton pump inhibitors for chronic gastroesophageal reflux disease: An Update. Curr. Drug Res. Rev., 2023, 15(3), 199-206.
[http://dx.doi.org/10.2174/2589977515666230221160449] [PMID: 36824005]
[http://dx.doi.org/10.2174/2589977515666230221160449] [PMID: 36824005]
[9]
Othman, F.; Card, T.R.; Crooks, C.J. Proton pump inhibitor prescribing patterns in the UK: A primary care database study. Pharmacoepidemiol. Drug Saf., 2016, 25(9), 1079-1087.
[http://dx.doi.org/10.1002/pds.4043] [PMID: 27255671]
[http://dx.doi.org/10.1002/pds.4043] [PMID: 27255671]
[10]
Sachar, H.; Vaidya, K.; Laine, L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: A systematic review and meta-analysis. JAMA Intern. Med., 2014, 174(11), 1755-1762.
[http://dx.doi.org/10.1001/jamainternmed.2014.4056] [PMID: 25201154]
[http://dx.doi.org/10.1001/jamainternmed.2014.4056] [PMID: 25201154]
[11]
Kristl, A. Acido-basic properties of proton pump inhibitors in aqueous solutions. Drug Dev. Ind. Pharm., 2009, 35(1), 114-117.
[http://dx.doi.org/10.1080/03639040802220284] [PMID: 18720145]
[http://dx.doi.org/10.1080/03639040802220284] [PMID: 18720145]
[12]
Scarpignato, C.; Gatta, L.; Zullo, A.; Blandizzi, C. Effective and safe proton pump inhibitor therapy in acid-related diseases – A position paper addressing benefits and potential harms of acid suppression. BMC Med., 2016, 14(1), 179.
[http://dx.doi.org/10.1186/s12916-016-0718-z] [PMID: 27825371]
[http://dx.doi.org/10.1186/s12916-016-0718-z] [PMID: 27825371]
[13]
Schnoll-Sussman, F.; Niec, R.; Katz, P.O. Proton pump inhibitors: The good, bad, and ugly. Gastrointest. Endosc. Clin. N. Am., 2020, 30(2), 239-251.
[http://dx.doi.org/10.1016/j.giec.2019.12.005] [PMID: 32146944]
[http://dx.doi.org/10.1016/j.giec.2019.12.005] [PMID: 32146944]
[14]
Lassalle, M.; Le Tri, T.; Bardou, M.; Biour, M.; Kirchgesner, J.; Rouby, F.; Dumarcet, N.; Zureik, M.; Dray-Spira, R. Use of proton pump inhibitors in adults in France: A nationwide drug utilization study. Eur. J. Clin. Pharmacol., 2020, 76(3), 449-457.
[http://dx.doi.org/10.1007/s00228-019-02810-1] [PMID: 31838548]
[http://dx.doi.org/10.1007/s00228-019-02810-1] [PMID: 31838548]
[15]
Luo, H.; Fan, Q.; Bian, T.; Li, X.; Chen, K.; Zhang, Q.; Wei, Y.; Xiao, Y.; Li, Y. Awareness, attitude and behavior regarding proton pump inhibitor among medical staff in the Southwest of China. BMC Health Serv. Res., 2019, 19(1), 880.
[http://dx.doi.org/10.1186/s12913-019-4725-6] [PMID: 31752835]
[http://dx.doi.org/10.1186/s12913-019-4725-6] [PMID: 31752835]
[16]
Worden, J.C.; Hanna, K.S. Optimizing proton pump inhibitor therapy for treatment of nonvariceal upper gastrointestinal bleeding. Am. J. Health Syst. Pharm., 2017, 74(3), 109-116.
[http://dx.doi.org/10.2146/ajhp151032] [PMID: 28122752]
[http://dx.doi.org/10.2146/ajhp151032] [PMID: 28122752]
[17]
Gupta, A.; Akhtar, J.; Rastogi, K.C.; Badruddeen, B.; Khan, M.I.; Ahmad, M.; Kumar, S. Enteric coated microgranules of pantoprazole sodium in gastroesophageal reflux disease. Ann. Phytomed., 2023, 12(1), 407-412.
[http://dx.doi.org/10.54085/ap.2023.12.1.97]
[http://dx.doi.org/10.54085/ap.2023.12.1.97]
[18]
Sengupta, P.; Chatterjee, B.; Tekade, R.K. Current regulatory requirements and practical approaches for stability analysis of pharmaceutical products: A comprehensive review. Int. J. Pharm., 2018, 543(1-2), 328-344.
[http://dx.doi.org/10.1016/j.ijpharm.2018.04.007] [PMID: 29635054]
[http://dx.doi.org/10.1016/j.ijpharm.2018.04.007] [PMID: 29635054]
[19]
ICH guidelines, Q1A (R2): Stability Testing of New Drug Substances and Products (revision 2), International Conference on Harmonization.. 2003. Available from:
http://www.fda.gov/downloads/Regulatory Information/Guidances/ucm128204
[20]
González-González, O.; Ramirez, I.O.; Ramirez, B.I.; O’Connell, P.; Ballesteros, M.P.; Torrado, J.J.; Serrano, D.R. Drug Stability: ICH versus accelerated predictive stability studies. Pharmaceutics, 2022, 14(11), 2324.
[http://dx.doi.org/10.3390/pharmaceutics14112324] [PMID: 36365143]
[http://dx.doi.org/10.3390/pharmaceutics14112324] [PMID: 36365143]
[21]
Chew, Y.L.; Khor, M.A.; Lim, Y.Y. Choices of chromatographic methods as stability indicating assays for pharmaceutical products: A review. Heliyon, 2021, 7(3), e06553.
[http://dx.doi.org/10.1016/j.heliyon.2021.e06553] [PMID: 33855234]
[http://dx.doi.org/10.1016/j.heliyon.2021.e06553] [PMID: 33855234]
[22]
Chafetz, L. Stability-indicating assay methods for drugs and their dosage forms. J. Pharm. Sci., 1971, 60(3), 335-345.
[http://dx.doi.org/10.1002/jps.2600600302] [PMID: 5572109]
[http://dx.doi.org/10.1002/jps.2600600302] [PMID: 5572109]
[23]
Blessy, M.; Patel, R.D.; Prajapati, P.N.; Agrawal, Y.K. Development of forced degradation and stability indicating studies of drugs—A review. J. Pharm. Anal., 2014, 4(3), 159-165.
[http://dx.doi.org/10.1016/j.jpha.2013.09.003] [PMID: 29403878]
[http://dx.doi.org/10.1016/j.jpha.2013.09.003] [PMID: 29403878]
[24]
Speiser, P. Haltbarkeit und haltbarmachung der arzneimittel. V. Pharm. Acta Helv., 1968, 43(2), 65-78.
[PMID: 5720916]
[PMID: 5720916]
[25]
Bakshi, M.; Singh, S. Development of validated stability-indicating assay methods—critical review. J. Pharm. Biomed. Anal., 2002, 28(6), 1011-1040.
[http://dx.doi.org/10.1016/S0731-7085(02)00047-X] [PMID: 12049968]
[http://dx.doi.org/10.1016/S0731-7085(02)00047-X] [PMID: 12049968]
[26]
Chen, L.; Wu, Y.; Guan, Y.; Jin, C.; Zhu, W.; Yang, M. Analysis of the high-performance liquid chromatography fingerprints and quantitative analysis of multicomponents by single marker of products of fermented cordyceps sinensis. J. Anal. Methods Chem., 2018, 2018(43), 1-9.
[http://dx.doi.org/10.1155/2018/5943914] [PMID: 29850373]
[http://dx.doi.org/10.1155/2018/5943914] [PMID: 29850373]
[27]
Sahu, P.K.; Ramisetti, N.R.; Cecchi, T.; Swain, S.; Patro, C.S.; Panda, J. An overview of experimental designs in HPLC method development and validation. J. Pharm. Biomed. Anal., 2018, 147, 590-611.
[http://dx.doi.org/10.1016/j.jpba.2017.05.006] [PMID: 28579052]
[http://dx.doi.org/10.1016/j.jpba.2017.05.006] [PMID: 28579052]
[28]
Zhao, P.; Deng, M.; Huang, P.; Yu, J.; Guo, X.; Zhao, L. Solid-phase extraction combined with dispersive liquid-liquid microextraction and chiral liquid chromatography-tandem mass spectrometry for the simultaneous enantioselective determination of representative proton-pump inhibitors in water samples. Anal. Bioanal. Chem., 2016, 408(23), 6381-6392.
[http://dx.doi.org/10.1007/s00216-016-9753-z] [PMID: 27449644]
[http://dx.doi.org/10.1007/s00216-016-9753-z] [PMID: 27449644]
[29]
Polonini, H.C.; Silva, S.L.; Loures, S.; Almy, R.; Balland, A.; Brandão, M.A.F.; Ferreira, A.O. Compatibility of proton pump inhibitors in a preservative-free suspending vehicle. Eur. J. Hosp. Pharm. Sci. Pract., 2018, 25(3), 150-156.
[http://dx.doi.org/10.1136/ejhpharm-2016-001034] [PMID: 31157010]
[http://dx.doi.org/10.1136/ejhpharm-2016-001034] [PMID: 31157010]
[30]
Rajab, A.; Touma, M.; Rudler, H.; Afonso, C.; Seuleiman, M. Slow, spontaneous degradation of lansoprazole, omeprazole and pantoprazole tablets: isolation and structural characterization of the toxic antioxidants 3H-benzimidazole-2-thiones. Pharmazie, 2013, 68(9), 749-754.
[PMID: 24147343]
[PMID: 24147343]
[31]
Ashour, S.; Omar, S. A modified high-performance liquid chromatographic method for the analysis of pantoprazole sodium in pharmaceutical dosage forms using lansoprazole as internal standard. Arab. J. Chem., 2016, 9(Suppl. 1), S114-S119.
[http://dx.doi.org/10.1016/j.arabjc.2011.02.010]
[http://dx.doi.org/10.1016/j.arabjc.2011.02.010]
[32]
Addo, R.T.; Davis, K.; Ubale, R.; Owen, J.S.; Watkins, E.B. Development and validation of a UPLC method for rapid and simultaneous analysis of proton pump inhibitors. AAPS PharmSciTech, 2015, 16(1), 30-34.
[http://dx.doi.org/10.1208/s12249-014-0207-7] [PMID: 25160675]
[http://dx.doi.org/10.1208/s12249-014-0207-7] [PMID: 25160675]
[33]
Perumal, S.S.; Ekambaram, S.P.; Raja, S. Analytical method development and validation of simultaneous estimation of rabeprazole, pantoprazole, and itopride by reverse-phase high-performance liquid chromatography. Yao Wu Shi Pin Fen Xi, 2014, 22(4), 520-526.
[PMID: 28911469]
[PMID: 28911469]
[34]
Chennuru, L.N.; Choppari, T.; Duvvuri, S.; Dubey, P.K. Enantiomeric separation of proton pump inhibitors on new generation chiral columns using LC and supercritical fluid chromatography. J. Sep. Sci., 2013, 36(18), 3004-3010.
[http://dx.doi.org/10.1002/jssc.201300419] [PMID: 23857714]
[http://dx.doi.org/10.1002/jssc.201300419] [PMID: 23857714]
[35]
Ekpe, A.; Jacobsen, T. Effect of various salts on the stability of lansoprazole, omeprazole, and pantoprazole as determined by high-performance liquid chromatography. Drug Dev. Ind. Pharm., 1999, 25(9), 1057-1065.
[http://dx.doi.org/10.1081/DDC-100102270] [PMID: 10518247]
[http://dx.doi.org/10.1081/DDC-100102270] [PMID: 10518247]
[36]
Pakinaz, Y Square wave stripping voltammetric determination of pantoprazole in rabbit plasma using surfactant-based pencil graphite electrode. J. Anal. Chem., 2019, 7496, 609-616.
[37]
Ramakrishna, N.V.S.; Vishwottam, K.N.; Wishu, S.; Koteshwara, M. High-performance liquid chromatography method for the quantification of pantoprazole in human plasma. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2005, 822(1-2), 326-329.
[http://dx.doi.org/10.1016/j.jchromb.2005.06.011] [PMID: 16005696]
[http://dx.doi.org/10.1016/j.jchromb.2005.06.011] [PMID: 16005696]
[38]
Rajesh, S. Stability-indicating rp-hplc method for analysis of paracetamol and tramadol in a pharmaceutical dosage form. J. Chem., 2012, 9.
[39]
Emami, J.; Rezazadeh, M.; Kalani, M. Quantification of pantoprazole by high performance liquid chromatography (hplc) method: In vitro and in vivo applications. J. Liq. Chromatogr. Relat. Technol., 2014, 37(5), 681-695.
[http://dx.doi.org/10.1080/10826076.2012.758137]
[http://dx.doi.org/10.1080/10826076.2012.758137]
[40]
Mansour, A.M.; Sorour, O.M. High performance liquid chromatographic determination of pantoprazole in tablet dosage form. Chromatographia, 2001, 53(S1), S478-S479.
[http://dx.doi.org/10.1007/BF02490382]
[http://dx.doi.org/10.1007/BF02490382]
[41]
El-Kommos, M.E.; Khashaba, P.Y.; Ali, H.R.H.; El-Wekil, M.M. Different chromatographic and electrophoretic methods for analysis of proton pump inhibitors (PPIs): A Review. J. Liq. Chromatogr. Relat. Technol., 2015, 38(18), 1639-1659.
[http://dx.doi.org/10.1080/10826076.2015.1079722]
[http://dx.doi.org/10.1080/10826076.2015.1079722]
[42]
Moustafa, A.A.M. Spectrophotometric methods for the determination of lansoprazole and pantoprazole sodium sesquihydrate. J. Pharm. Biomed. Anal., 2000, 22(1), 45-58.
[http://dx.doi.org/10.1016/S0731-7085(99)00275-7] [PMID: 10727122]
[http://dx.doi.org/10.1016/S0731-7085(99)00275-7] [PMID: 10727122]
[43]
Noubarani, M.; Keyhanfar, F.; Motevalian, M.; Mahmoudian, M. Improved HPLC method for determination of four PPIs, omeprazole, pantoprazole, lansoprazole and rabeprazole in human plasma. J. Pharm. Pharm. Sci., 2010, 13(1), 1-10.
[http://dx.doi.org/10.18433/J3GP4Q] [PMID: 20456825]
[http://dx.doi.org/10.18433/J3GP4Q] [PMID: 20456825]
[44]
Zhang, Y.; Chen, X.; Gu, Q.; Zhong, D. Quantification of rabeprazole in human plasma by liquid chromatography-tandem mass spectrometry. Anal. Chim. Acta, 2004, 523(2), 171-175.
[http://dx.doi.org/10.1016/j.aca.2004.07.023]
[http://dx.doi.org/10.1016/j.aca.2004.07.023]
[45]
Yousaf, A.; Kim, D.; Choi, H-G.; Oh, E. Validation of a highly sensitive RP-HPLC method for quantification of fenofibrate in pure and pharmaceutical dosage forms. Curr. Pharm. Anal., 2014, 10(2), 97-104.
[http://dx.doi.org/10.2174/1573412910999140113115903]
[http://dx.doi.org/10.2174/1573412910999140113115903]
[46]
Chang, W.H.; Liu, P.Y.; Jiang, Y.T.; Hsu, Y-H.H. A sensitive chromatographic method for hyaluronate quantification applied to analyze the desorption behavior on contact lenses. Curr. Pharm. Anal., 2020, 16(6), 782-791.
[http://dx.doi.org/10.2174/1573412915666190304142952]
[http://dx.doi.org/10.2174/1573412915666190304142952]
[47]
Qiu, H. Simultaneous determination of koumine and gelsemine in human plasma using HPLC-UV assay and its clinical application. Curr. Pharm. Anal., 2019, 15(6)
[http://dx.doi.org/10.2174/1573412915666190222161942]
[http://dx.doi.org/10.2174/1573412915666190222161942]
[48]
Zozina, V.I.; Melnikov, E.S.; Goroshko, O.A.; Krasnykh, L.M.; Kukes, V.G. Analytical method development for coq10 determination in human plasma using HPLC-UV and HPLC/MS/MS. Curr. Pharm. Anal., 2019, 15(7), 795-807.
[http://dx.doi.org/10.2174/1573412915666190328215854]
[http://dx.doi.org/10.2174/1573412915666190328215854]
[49]
Bhaskara, B.L.; Anil Kumar, U.R.; Basavaiah, K. Sensitive liquid chromatography-tandem mass spectrometry method for the determination of pantoprazole sodium in human urine. Arab. J. Chem., 2011, 4(2), 163-168.
[http://dx.doi.org/10.1016/j.arabjc.2010.06.033]
[http://dx.doi.org/10.1016/j.arabjc.2010.06.033]
[50]
El-Sherif, Z.A.; Mohamed, A.O.; El-Bardicy, M.G.; El-Tarras, M.F. Reversed-phase high performance liquid chromatographic method for the determination of lansoprazole, omeprazole and pantoprazole sodium sesquihydrate in presence of their Acid-induced degradation products. Chem. Pharm. Bull., 2006, 54(6), 814-818.
[http://dx.doi.org/10.1248/cpb.54.814] [PMID: 16755049]
[http://dx.doi.org/10.1248/cpb.54.814] [PMID: 16755049]
[51]
Ghadge, M.R.; Tambe, V.S.; Darade, P.G. Analysis of proton pump inhibitors in bulk and in different dosage forms -a review. Int. J. Pharma. Res. Rev., 2014, 3(1), 45-57.
[52]
Vaithiyanathan, S.J.; Rajappan, M.; Kannappan, V. Stabilityindicating HPLC method for the simultaneous determination of pantoprazole, rabeprazole, lansoprazole and domperidone from their combination dosage forms. Int. J. Drug Dev. Res., 2011, 3(4), 323-335.
[53]
Mutalabisin, F.; Helaluddin, A.B.M.; Sengupta, P.; Mohamed, F.; Chatterjee, B. Quantitation of pregabalin by HPLC-UV method using ninhydrin derivatization: development and validation. Curr. Pharm. Anal., 2021, 17(1), 165-171.
[http://dx.doi.org/10.2174/1573412916666191114120213]
[http://dx.doi.org/10.2174/1573412916666191114120213]
[54]
Patel, B.H.; Suhagia, B.N.; Patel, M.M.; Patel, J.R. Determination of pantoprazole, rabeprazole, esomeprazole, domperidone and itopride in pharmaceutical products by reversed phase liquid chromatography using single mobile phase. Chromatographia, 2007, 65(11-12), 743-748.
[http://dx.doi.org/10.1365/s10337-007-0220-z]
[http://dx.doi.org/10.1365/s10337-007-0220-z]
[55]
Zendelovska, D.; Atanasovska, E.; Gjorgjievska, K.; Pavlovska, K.; Jakjovski, K.; Zafirov, D.; Trojacanec, J. A new solid-phase extraction method for determination of pantoprazole in human plasma using high-performance liquid chromatography. Open Access Maced. J. Med. Sci., 2019, 7(11), 1757-1761.
[http://dx.doi.org/10.3889/oamjms.2019.237] [PMID: 31316654]
[http://dx.doi.org/10.3889/oamjms.2019.237] [PMID: 31316654]
[56]
Chen, F.; He, X.; Fang, B.; Wang, S. Simultaneous quantitative analysis of six proton-pump inhibitors with a single marker and evaluation of stability of investigated drugs in polypropylene syringes for continuous infusion use. Drug Des. Devel. Ther., 2020, 14, 5689-5698.
[http://dx.doi.org/10.2147/DDDT.S279302] [PMID: 33380789]
[http://dx.doi.org/10.2147/DDDT.S279302] [PMID: 33380789]
