Comparison of UV - and Derivative-Spectrophotometric and HPTLC UVDensitometric Methods for the Determination of Amrinone and Milrinone in Bulk Drugs

Author(s): Marcin Gackowski*, Marcin Koba, Stefan Kruszewski

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 3 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Spectrophotometry and thin layer chromatography have been commonly applied in pharmaceutical analysis for many years due to low cost, simplicity and short time of execution. Moreover, the latest modifications including automation of those methods have made them very effective and easy to perform, therefore, the new UV- and derivative spectrophotometry as well as high performance thin layer chromatography UV-densitometric (HPTLC) methods for the routine estimation of amrinone and milrinone in pharmaceutical formulation have been developed and compared in this work since European Pharmacopoeia 9.0 has yet incorporated in an analytical monograph a method for quantification of those compounds.

Methods: For the first method the best conditions for quantification were achieved by measuring the lengths between two extrema (peak-to-peak amplitudes) 252 and 277 nm in UV spectra of standard solutions of amrinone and a signal at 288 nm of the first derivative spectra of standard solutions of milrinone. The linearity between D252-277 signal and concentration of amironone and 1D288 signal of milrinone in the same range of 5.0-25.0 μg ml/ml in DMSO:methanol (1:3 v/v) solutions presents the square correlation coefficient (r2) of 0,9997 and 0.9991, respectively. The second method was founded on HPTLC on silica plates, 1,4-dioxane:hexane (100:1.5) as a mobile phase and densitometric scanning at 252 nm for amrinone and at 271 nm for milrinone.

Results: The assays were linear over the concentration range of 0,25-5.0 μg per spot (r2=0,9959) and 0,25-10.0 μg per spot (r2=0,9970) for amrinone and milrinone, respectively. The mean recoveries percentage were 99.81 and 100,34 for amrinone as well as 99,58 and 99.46 for milrinone, obtained with spectrophotometry and HPTLC, respectively.

Conclusion: The comparison between two elaborated methods leads to the conclusion that UV and derivative spectrophotometry is more precise and gives better recovery, and that is why it should be applied for routine estimation of amrinone and milrinone in bulk drug, pharmaceutical forms and for therapeutic monitoring of the drug.

Keywords: Amrinone, milrinone, High Performance Thin Layer Chromatography (HPTLC), Ultraviolet (UV)-derivative spectrophotometry, UV-densitometry, bulk drug.

Asif, M. Phosphodiesterase-III inhibitors amrinone and milrinone on epilepsy and cardiovascular activities. N. Am. J. Med. Sci., 2012, 4(10), 499-502.
[] [PMID: 23112975]
De Luca, L.; Proietti, P.; Palombaro, G.L.; Battagliese, A.; Celotto, A.; Bucciarelli Ducci, C.; Fedele, F. New positive inotropic agents in the treatment of left ventricular dysfunction. Ital. Heart J., 2004, 5(Suppl. 6), 63S-67S.
[PMID: 15185917]
Wojtczaks, A.; Codye, V. Structural aspects of inotropic bipyridine binding. 1993, 268(9), 6202-6206.
Tyagi, M.G. Evaluation of cyclic nucleotide phosphodiesterase III inhibitors in animal models of epilepsy 2008, 19(1), 13-17.
Pattan, S.R.; Purohit, S.S.; Rasal, V.P.; Mallya, S. Synthesis and pharmacological screening of some 1, 4-dihydropyridine and their derivatives for anticonvulsant activity. Indian J. Chem. Sect. B, 2008, 47(April), 626-629.
Kikura, M.; Sato, S. Effects of preemptive therapy with milrinone or amrinone on perioperative platelet function and haemostasis in patients undergoing coronary bypass grafting. Platelets, 2003, 14(5), 277-282.
[] [PMID: 12944243]
Healthcare., C. of E. . E. P. C. . E. D. for the Q. of M. &. European Pharmacopoeia 9.0 Strasbourg. 2017.
Butterworth, J.F. IV; Hines, R.L.; Royster, R.L.; James, R.L. A pharmacokinetic and pharmacodynamic evaluation of milrinone in adults undergoing cardiac surgery. Anesth. Analg., 1995, 81(4), 783-792.
[PMID: 7574011]
Siddiqui, M.R.; AlOthman, Z.A.; Rahman, N. Analytical Techniques in Pharmaceutical Analysis: A Review. Arab. J. Chem., 2017, 10, S1409-S1421.
Alothman, Z.A.; Rahman, N.; Siddiqui, M.R. Review on pharmaceutical impurities, stability studies and degradation products: An analytical approach. Rev. Adv. Sci. Eng., 2013, 2(2), 155-166.
Rahman, N.; Azmi, S.N.H.; Wu, H-F. The importance of impurity analysis in pharmaceutical products: An integrated approach. Accredit. Qual. Assur., 2006, 11(1), 69-74.
Magiera, S.; Baranowska, I.; Kusa, J. Development and validation of UHPLC-ESI-MS/MS method for the determination of selected cardiovascular drugs, polyphenols and their metabolites in human urine. Talanta, 2012, 89, 47-56.
[] [PMID: 22284458]
Gavra, P.; Nguyen, A.Q.N.; Beauregard, N.; Denault, A.Y.; Varin, F. High-performance liquid chromatography assay using ultraviolet detection for urinary quantification of milrinone concentrations in cardiac surgery patients undergoing cardiopulmonary bypass. Biomed. Chromatogr., 2014, 28(8), 1084-1089.
[] [PMID: 24522977]
Nguyen, A.Q.N.; Théorêt, Y.; Chen, C.; Denault, A.; Varin, F. High performance liquid chromatography using UV detection for the quantification of milrinone in plasma: improved sensitivity for inhalation. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2009, 877(7), 657-660.
[] [PMID: 19201666]
Bhaskar, V.V.; Gurupadayya, B.M.; Manohara, Y.N. HPLC and UV Spectrophotometric Determination of Amrinone Lactate, 2007, 19(7), 5049-5056.
Siddiqui, M.R.; Tariq, A.; Ahmad, A.; Chaudhary, M.; Shrivastav, S.M.; Singh, R.K. Application of DDQ and P-chloranilic acid for the spectrophotometric estimation of milrinone in pharmaceutical formulations. Asian J. Sci. Res., 2009, 2(3), 135-145.
Koba, M.; Koba, K.; Baczek, T. Determination of oxazepam in pharmaceutical formulation by HPTLC UV-densitometric and UV-derivative spectrophotometry methods. Anal. Lett., 2009, 42(12), 1831-1843.
Koba, M.; Koba, K. Ba czek, T. UV densitometric HPTLC method for analysis of nitrazepam in pharmaceutical formulations. J. Planar Chromatogr. Mod. TLC, 2011, 24(1), 44-47.
Koba, M. Application of HPTLC and LC-MS methods for determination of topiramate in pharmaceutical formulations. Curr. Pharm. Anal., 2012, 8(1), 44-48.
Gackowski, M.; Koba, M. Determination of lormetazepam in tablets using high-performance liquid chromatography, and derivative spectrophotometry methods. J. Planar Chromatogr. Mod. TLC, 2018, 31, 235-242.
Teva Canada Limited. Product Monograph Milrinone Injection., 2014.
Guidelines for Standard Method Performance Requirements (Appendix F); AOAC Off. Methods Anal., 2012, 1-17.
Koba, M.; Koba, K.; Baczek, T. UV Densitometric HPTLC Method for Analysis of Nitrazepam in Pharmaceutical Formulations; , 2011, Vol. 24, .
Koba, M. Determination of lamotrigine in tablets using HPTLC, HPLC, and derivative spectrophotometry methods. J. Liq. Chromatogr. Relat. Technol., 2013, 36(4), 537-548.
Kus, S.; Marczenko, Z.; Obarski, N. Derivative UV-VIS spectrophotometry in analytical chemistry. Chem. Anal. (Pol.), 1996, 41(41), 899-927.
Rashmin, P.; Mrunali, P.; Nitin, D.; Nidhi, D.; Bharat, P. HPTLC Method development and validation: Strategy to minimize methodological failures. Yao Wu Shi Pin Fen Xi, 2012, 20(4), 794-804.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 30 March, 2020
Page: [246 - 253]
Pages: 8
DOI: 10.2174/1573412914666180627141659
Price: $65

Article Metrics

PDF: 18
PRC: 1