Two chemometrics-assisted UV spectrophotometric methods were proposed for the resolution of ternary mixtures without any chemical pretreatment. The first method is based on modification of H-point standard addition method which permits simultaneous analysis of three species from a unique calibration set by making the simultaneous addition of the three analytes. Quotient between the spectra of aspirin, atorvastatin, and clopidogrel was obtained and the results showed that simultaneous determination of aspirin, atorvastatin, and clopidogrel can be obeyed in the linear range 2.5–20？μg？mL？1 of aspirin, 2.5–17.5？μg？mL？1 of atorvastatin, and 2.5–20？μg？mL？1 of clopidogrel in ternary mixture. The second method is based on the combination of the first derivative spectra and Cramer's matrix rule. In the matrix calculation, clopidogrel has zero crossing point at 316.8 and 212？nm, while for atorvastatin the zero crossing point at 250？nm where the matrix is greatly simplified and easily solved. The linear concentration ranges were 2.5–20？μg？mL？1 aspirin, 2.5–17.5？μg？mL？1 atorvastatin and 2.5–20？μg？mL？1 clopidogrel in ternary mixtures. The results proved that the simultaneous determination of aspirin, atorvastatin, and clopidogrel could be obeyed. Both methods were applied for capsules containing the three ingredients and results were in good concordance with alternative liquid chromatography. 1. Introduction Aspirin (ASP, acetylsalicylic acid) is used as an analgesic, antipyretic, anti-inflammatory medication and an antiplatelet agent. For clopidogrel bisulphate (CLOP), chemically it is methyl (+)-(S)-α-(2-chlorophenyl)-6,7-dihydrothieno[3, 2-c]pyridine-5(4H)acetate sulfate (1？:？1) and is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. Atorvastatin calcium (ATOR), [R- ]-2-(4-fluorophenyl)-β,δ,-dihydroxy-5-(1-methylethyl)-3-phenyl-4 [(phenylamino)carbonyl]-lH-pyrrole-1-heptanoic acid, calcium salt (2？:？1) trihydrate is an inhibitor of 3 hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Chemical structures of ASP, CLOP, and ATOR are shown in Scheme 1. Scheme 1: Aspirin (a), clopidogrel (b), and atorvastatin (c). A combination of ASP, CLOP, and ATOR drugs is available in the market as capsules. The ternary combination is used for atherosclerotic patients suffering from various heart diseases. Clinical trials showed that combination therapy when used in dyslipidaemic patient with coronary heart disease reduced cardiovascular events. The official
References
[1]
US Pharmacopoeia, US Pharmacopial Convention, Rockville, Md, USA, 23rd edition, 1955.
[2]
Indian Pharmacopoeia, vol. 2, The Controller of Publications, Government of India, New Delhi, India, 1996.
[3]
British Pharmacopoeia, vol. 2, HMSO Publication Centre, London, UK, 1993.
[4]
Martindale: The Complete Drug Reference, Pharmaceutical Press, London, UK, 35th edition, 2007.
[5]
S. Singh, N. Dubey, and D. K. Jain, “Simultaneous estimation of atorvastatin, clopidogrel and aspirin in capsule dosage forms using UV-spectroscopy,” Asian Journal of Research in Chemistry, vol. 3, no. 4, pp. 885–887, 2010.
[6]
S. Londhe, S. Mulgund, R. Deshmukh, and K. Jain, “Simultaneous HPTLC analysis of aspirin, atorvastatin calcium and clopidogrel bisulphate in the bulk drug and in capsules,” Acta Chromatographica, vol. 22, no. 2, pp. 297–305, 2010.
[7]
S. V. Londhe, R. S. Deshmukh, S. V. Mulgund, and K. S. Jain, “Development and validation of a reversed-phase HPLC method for simultaneous determination of aspirin, atorvastatin calcium and clopidogrel bisulphate in capsules,” Indian Journal of Pharmaceutical Sciences, vol. 73, no. 1, pp. 23–29, 2011.
[8]
H. O. Kaila, M. A. Ambasana, and A. K. Shah, “A Simple and rapid ultra-performance liquid chromatographic assay method for the simultaneous determination of aspirin, clopidogrel bisulphate and atorvastatin calcium in capsule dosage form,” International Journal of ChemTech Research, vol. 3, no. 1, pp. 459–465, 2011.
[9]
H. J. Panchal, B. N. Suhagia, N. J. Patel, I. S. Rathod, and B. H. Patel, “Simultaneous estimation of atorvastatin calcium, ramipril and aspirin in capsule dosage form by RP-LC,” Chromatographia, vol. 69, no. 1-2, pp. 91–95, 2009.
[10]
K. Alla, “A stability-indicating LC method for the simultaneous determination of metoprolol, atorvastatin and ramipril in combined pharmaceutical dosage form,” Journal of AOAC International, vol. 90, pp. 1547–1553, 2007.
[11]
F. Salinas, J. J. B. Nevado, and A. E. Mansilla, “A new spectrophotometric method for quantitative multicomponent analysis resolution of mixtures of salicylic and salicyluric acids,” Talanta, vol. 37, no. 3, pp. 347–351, 1990.
[12]
J. J. B. Nevado, C. G. Cabanillas, and F. Salinas, “Spectrophotometric resolution of ternary mixtures of salicylaldehyde, 3-hydroxybenzaldehyde and 4-hydroxybenzaldehyde by the derivative ratio spectrum-zero crossing method,” Talanta, vol. 39, no. 5, pp. 547–553, 1992.
[13]
E. Din？ and F. Onur, “Application of a new spectrophotometric method for the analysis of a ternary mixture containing metamizol, paracetamol and caffeine in tablets,” Analytica Chimica Acta, vol. 359, no. 1-2, pp. 93–106, 1998.
[14]
R. Hajian and N. Afshari, “The spectrophotometric multicomponent analysis of a ternary mixture of ibuprofen, caffeine and paracetamol by the combination of double divisor-ratio spectra derivative and H-point standard addition method,” E-Journal of Chemistry, vol. 9, no. 3, pp. 1153–1164, 2012.
[15]
F. Bosch-Reig and P. Campins-Falco, “H-point standard additions method part 1 fundamentals and application to analytical spectroscopy,” The Analyst, vol. 113, no. 7, pp. 1011–1016, 1988.
[16]
P. Campins-Falco, F. Bosch-Reig, and A. M. Benet, “Spectrophotometric analysis of mixtures of two components with extensively or completely overlapping spectra by the H-point standard additions method,” Fresenius' Journal of Analytical Chemistry, vol. 338, no. 1, pp. 16–21, 1990.
[17]
P. Campins-Falco, F. Bosch-Reig, and J. Verdu-Andres, “Evaluation and elimination of the ‘blank bias error’ using the H-point standard addition method. Application to spectrophotometric determinations using absorbent blank,” Analytica Chimica Acta, vol. 270, no. 1, pp. 253–265, 1992.
[18]
F. Bosch-Reig, J. Verdú-Andrés, P. Campíns-Falcó, and C. Molíns-Legua, “Study of the behaviour of the absorbent blanks in analytical procedures by using the H-Point standard additions method (HPSAM),” Talanta, vol. 41, no. 1, pp. 39–52, 1994.
[19]
H. Abdollahi, “Simultaneous spectrophotometric determination of chromium(VI) and iron(III) with chromogenic mixed reagents by H-point standard addition method and partial least squares regression,” Analytica Chimica Acta, vol. 442, no. 2, pp. 327–336, 2001.
[20]
R. Hajian, N. Shams, and A. Rad, “Application of H-point standard addition method for simultaneous spectrophotometric determination of hydrochlorothiazide and propranolol,” Journal of the Brazilian Chemical Society, vol. 20, no. 5, pp. 860–865, 2009.
[21]
M. M. Issa, R. N. Nejem, A. A. Shanab, and N. T. Shaat, “Kinetic simultaneous spectrophotometric determination of paracetamol and ibuprofen using H-point standard addition method,” Journal of Chemical Pharmaceutical Research, vol. 4, no. 7, pp. 3535–3540, 2012.
[22]
K. Lakshmi and S. Lakshmi, “Simultaneous spectrophotometric determination of valsartan and hydrochlorothiazide by H-point standard addition method and partial least squares regression,” Acta Pharmaceutica, vol. 61, no. 1, pp. 37–50, 2011.
[23]
M. M. Issa, R. M. Nejem, A. A. Shanab, and N. T. Shaat, “Kinetic spectrophotometric H-point standard addition method for the simultaneous determination of diloxanide furoate and metronidazole in binary mixtures and biological fluids,” Spectrochimica Acta A, vol. 114, pp. 592–598, 2013.
[24]
P. Campíns-Falcó, J. Verdú-Andrés, and F. Bosch-Reig, “H-point standard additions method for resolution of binary mixtures with simultaneous addition of both analytes,” Analytica Chimica Acta, vol. 315, no. 3, pp. 267–278, 1995.
[25]
M. Hasani, L. Yaghoubi, and H. Abdollahi, “H-point standard addition method for simultaneous determination of Fe(II), Co(II) and Cu(II) in micellar media with simultaneous addition of three analytes,” Talanta, vol. 68, no. 5, pp. 1528–1535, 2006.
[26]
H. G. Charlotte and T. L. Threlfall, UV-Vis Spectroscopy and Its Applications, Springer, New York, NY, USA, 1992.
[27]
V. Thomsen, D. Schatzlein, and D. Mercuro, “Limits of detection in spectroscopy,” Spectroscopy, vol. 18, no. 12, pp. 112–114, 2003.
