Application of potassium ferricyanide in the

spectrophotometric determination
of captopril
Shi Lei Wang
a,b
, Min Wang
a
, Quan Min Li
a,
*
a
College of Chemistry and Environmental Science, Henan Normal University, Xinxiang 453007, China
b
Department of Chemistry, Jiaozuo Teachers College, Jiaozuo 454000, China
Received 7 July 2008
Abstract
A novel method for the determination of captopril by spectrophotometer is described in this paper. The experiment is based on
the fact that Fe(III) is reduced to Fe(II) by captopril, then the in situ formed Fe(II) reacts with potassium ferricyanide to give the
soluble prussian blue at pH 4.00, and its maximal adsorption wavelength (l
max
) is 735 nm. Good linear relationship is obtained
between the absorbance and the concentration of captopril in the wide range of 0.0520 mg/mL. The linear regression equation is
A = 0.04314 + 0.11423C (mg/mL) with a correlation coefcient R = 0.9998. The detection limit (3s/k) is 0.04 mg/mL, the molar
absorption coefcient is 2.5 10
4
L/mol cm. By mensurating the absorbance of soluble prussian blue, the indirect determination of
captopril can be obtained. This method has been successfully applied to determination of captopril in pharmaceutical samples.
Analytical results obtained are satisfactory.
# 2008 Quan Min Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Potassium ferricyanide; Captopril; Prussian blue; Spectrophotometry
Captopril is the rst orally active angiotensin converting enzyme inhibitor. It is a well known drug applied to
the treatment of hypertension, coronary heart disease and congestive heart failure in clinical medicine.
Determination of captopril has previously been reported by capillary electrophoresis [1], ow injection analysis
[2], high performance liquid chromatography [3], kinetic spectrophotometry [4], FT-Raman spectroscopy [5],
voltammetry [6], gas chromatographymass spectrometry [7] etc. This paper presents a novel spectrophotometric
method for the determination of captopril by using potassium ferricyanide as chromogenic reagent. The
experiment indicates that Fe(III) can be reduced to Fe(II) by captopril at pH 4.00, then the in situ formed Fe(II)
reacts with K
3
[Fe(CN)
6
] to give the soluble prussian blue (KFe
III
[Fe
II
(CN)
6
], l
max
= 735 nm) [8a]. By
mensurating the absorbance of soluble prussian blue, the amount of captopril can be obtained indirectly. This
method is simple, rapid and economic, and is applied to the determine captopril in pharmaceutical samples
successfully.
www.elsevier.com/locate/cclet
Available online at www.sciencedirect.com
Chinese Chemical Letters 20 (2009) 8891
* Corresponding author.
E-mail address: mercury6068@126.com (Q.M. Li).
1001-8417/$ see front matter # 2008 Quan Min Li. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2008.10.021
1. Experimental
1.1. Reagents and apparatus
Captopril (Standard Drug, Beijing Jingfeng Pharmaceutical Co., Ltd., Beijing, China) solution: 62.5 mg/mL, 0.5%
(w/v) K
3
[Fe(CN)
6
] (A.R., Beijing Chemical Plant, Beijing, China), 0.5% FeCl
3
(A.R., Tianjing Chemical Plant,
Tianjing, China), T6 UV/vis spectrophotometer (Beijing Purkinje General Instrument Co., Ltd., Beijing, China).
1.2. Procedure
Add 1.00 mL of 62.5 mg/mL captopril, 2.00 mL of 0.5% FeCl
3
, 1.00 mL of 0.5% K
3
[Fe(CN)
6
] to a 25 mL color
comparison tube. Dilute it to mark with distilled water and mix well (pH of the solution is 4.00). Stand for 30 min at
room temperature, then measure the absorbance at 735 nm against reagent blank.
2. Results and discussion
2.1. Absorption spectrum
According to the procedure, the absorption spectrum of the reaction product (soluble prussian blue) against reagent
blank, and of captopril, reagent blank against distilled water is recorded, respectively. It can be seen that the maximum
absorption peak of the soluble prussian blue (curve c) is at 735 nm. Whereas, the absorbance of reagent blank (curve b)
and captopril (curve a) are almost zero at 735 nm (Fig. 1).
2.2. Inuences of reaction time, the amount of FeCl
3
and K
3
[Fe(CN)
6
]
The effects of reaction time, the amount of FeCl
3
and K
3
[Fe(CN)
6
] on the absorbance are studied according to the
procedure, respectively. When reaction time is 30 min, the amount of 0.5% FeCl
3
and 0.5% K
3
[Fe(CN)
6
] are 2.00 and
1.00 mL, respectively, the absorbance gets to its maximum. And the maximal absorbance keeps unchanged within
10 min. Therefore, 30 min reaction time, 2.00 mL of FeCl
3
, 1.00 mL of K
3
[Fe(CN)
6
] are chosen as the optimum
conditions.
2.3. Inuence of amount of HCl
Effect of amount of HCl on absorbance is shown in Fig. 2. When 2.00 mol/L of HCl is added 0 mol/mL (pH of the
solution is 4.0), the absorbance is maximum. Then with the added amount of HCl increasing in the range of 0.10
1.40 mol/mL, the absorbance descends sharply. It is as result of that the reduce potential of captopril decreases along
with pH decreasing [8b]. That is, the ability that Fe(III) can be reduced to Fe(II) by captopril is declined, then leads to
the concentration of soluble prussian blue formed decline, and the absorbance descend. When pH of the solution is
above 4.00, Fe(III) can be formed to Fe(OH)
3
which interferes with determination of captopril. Therefore, the
absorbance is measured at pH 4.00.
S.L. Wang et al. / Chinese Chemical Letters 20 (2009) 8891 89
Fig. 1. Absorption spectrum. (a) Captopril, (b) reagent blank, and (c) prussian blue.
2.4. Inuence of organic solvent
The effects of different organic solvents on the absorbance are shown in Fig. 3. Contrasting with CH
3
CH
2
OH and
CH
3
OH, the effect of CH
3
COCH
3
on the absorbance is more remarkable. When the amount of CH
3
COCH
3
is added,
the absorbance is increased obviously. It seems reasonable that the polarity of CH
3
COCH
3
is less than that of CH
3
OH
and CH
3
CH
2
OH, and the stability constant of complex increases along with the polarity of organic solvent decreasing
[9]. Therefore, the stability constant of soluble prussian blue is maximal in the presence of CH
3
COCH
3
and the
absorbance is maximum.
2.5. Calibration curve
Good calibration curve of the concentration of captopril against the absorbance is observed. The linear equation is
A = 0.0431 + 0.114C (mg/mL) in the range of 0.05020.0 mg/mL with a correlation coefcient R = 0.9998, the e
735
is 2.50 10
4
L/mol cm. According to the procedure, the absorbance of solution of captopril (2.5 mg/mL)FeCl
3

K
3
[Fe(CN)
6
] is parallelly determined 11 times with the standard deviation (s) is 0.0014. Consequently, the detection
limit (3s/k) of this proposed method is found to be 0.04 mg/mL.
2.6. Reaction mechanism
It is reported that Fe(III) can be reduced to Fe(II) by thiol group (SH) of captopril (RSH) [10], then in
situ formed Fe(II) reacts with K
3
[Fe(CN)
6
] to give KFe
III
[Fe
II
(CN)
6
], and the mole ratio in the oxidation
S.L. Wang et al. / Chinese Chemical Letters 20 (2009) 8891 90
Fig. 3. Effect of organic solvent. Captopril: 62.5 mg, reaction temperature: room temperature, FeCl
3
(0.50%): 2.00 mL, K
3
[Fe(CN)
6
] (0.50%):
1.00 mL, reaction time: 30 min, total volume: 25 mL.
Fig. 2. Effect of HCl. Captopril: 62.5 mg, reaction temperature: room temperature, FeCl
3
(0.50%): 2.00 mL, K
3
[Fe(CN)
6
] (0.50%): 1.00 mL,
reaction time: 30 min, total volume: 25 mL.
reduction reaction of Fe(III) and captopril is 1:1. Therefore, it seems reasonable that the reaction mechanism is as
follows:
I. Fe(III) is reduced to Fe(II) by captopril:
2RSH 2FeIII ! 2FeII RS-SR 2H

II. The resultant Fe(II) reacts with K

3
[Fe(CN)
6
] to form the soluble prussian blue:
FeII K
3
Fe
III
CN
6
! KFe
III
Fe
II
CN
6

2.7. Inuence of potential interference

The effects of some familiar excipients, diluents substances and common ions on the determination of captopril are
investigated. The tolerance level is dened as an error less than 5%. A conclusion is drawn as follows: 200 mg/mL
starch; 125 mg/mL dextrose, sucrose, lactose, citric acid and fructose; 25 mg/mL glutamic acid, praline, serine,
leucine, glycin, lysine, tryptophan, tyrosine and arginine, 500 mg/mL Ca
2+
, Al
3+
, Zn
2+
, Ni
2+
, Pb
2+
, Co
2+
, Cd
2+
, Cr
3+
,
1500 mg/mL K
+
, Na
+
, SO
4
2
, NO
3

, F

, Cl

and Br

do not affect the determination of captopril.

2.8. Sample analysis
In order to demonstrate the performance of the described method, the determination of captopril in tablet samples is
carried out, the results are presented in Table 1.
References
[1] S. Hillaert, W. Van den Bossche, J. Pharm. Biomed. Anal. 21 (1999) 65.
[2] A. Economou, D.G. Themelis, G. Theodoridis, P.D. Tzanavaras, Anal. Chim. Acta 463 (2002) 249.
[3] F. Tache, A. Farca, A. Medvedovici, V. David, J. Pharm. Biomed. Anal. 28 (2002) 549.
[4] J.A.V. Prior, J.L.M. Santos, J.L.F.C. Lima, Anal. Chim. Acta 600 (2007) 183.
[5] S. Mazurek, R. Szostak, J. Pharm. Biomed. Anal. 40 (2006) 1225.
[6] H. Parham, B. Zargar. Talanta 65 (2005) 776.
[7] M.E. Franklin, R.S. Addison, P.V. Baker, W.D. Hooper, J. Chromatogr. B 705 (1998) 47.
[8] (a) Inorganic Chemistry(Part III), China Higher Education Press, Beijing, 2002, p.887.;
(b) Inorganic Chemistry(Part III), China Higher Education Press, Beijing, 2002, p.380.
[9] J.M. Pan, Y.S. Chen, H.T. Yan, Application of the Chromogenic Reagent in Metallurgical Analysis, Shanghai Science and Technology Press,
Shanghai, 1981, p. 53.
[10] F.G. Cheng, J. South-Central Univ. Nation 25 (2006) 28.
S.L. Wang et al. / Chinese Chemical Letters 20 (2009) 8891 91
Table 1
Determination results of samples and recovery (n = 5, t
0.05,4
= 2.78).
Sample Sample contents
(mg/mL)
Proposed method
(mg/mL)
Added
(mg/mL)
Total found
(mg/mL)
Recovery
(%)
Tablet
contents (%)
R.S.D.
(%)
1 2.50 2.48 1.00 3.47 99.0 12.99 0.20
2 2.50 2.51 2.00 4.52 100.5 13.18 0.17
3 2.50 2.49 3.00 5.48 99.7 13.08 0.19
4 2.50 2.52 4.00 6.53 100.2 13.14 0.36
5 2.50 2.49 5.00 7.53 100.8 13.22 0.60