265 

This work is licensed under a Creative Commons Attribution 4.0 International License 

IHJPAS. 37 (1) 2024 

Ibn Al-Haitham Journal for Pure and Applied Sciences 

Journal homepage: jih.uobaghdad.edu.iq 

PISSN: 1609-4042, EISSN: 2521-3407 

  

 

 

 

 

 

1Muntadhar Mohammed Jabbar*     2Elham Nghaimesh Mezaal   
1,2

Department of chemistry, College of Education for Pure Science Ibn Al-Haitham, University of Baghdad, 

Baghdad, Iraq. 

 

 

*Corresponding Author: muntadhar.jabbar2105m@ihcoedu.uobaghdad.edu.iq 

 

 

 

 

Abstract  

The determination of captopril (CAP) using a new continuous flow injection analysis (CFIA) 

method was given in this work CAP in its pure state and some of its pharmaceutical 

preparations. The technique can be described as simple, fast, sensitive, easy to operate, and low-

cost. The CAP reacted with ammonium ceric(IV) sulfate (ACS)2(NH4 )2SO4Ce(SO4)2. 3
1

2
H2O 

in an acidic medium and the reaction led to the formation of a white, slightly yellowish 

precipitate. The formed precipitate was studied using Ayah 6S×1-ST-2D Solar cell-CFI 

Analyzer, a through the reflection of accident light on the surfaces of the precipitate particles 

at (0-1800), expressed as the response of the transducer measured in (mV). Some chemical and 

physical parameters were studied to provide the optimal conditions for the study. The 

calibration curve within the range of (0.07-3.0) mmol/L was linear, with a correlation 

coefficient (r) value equal to (0.9983), and the percentage value of linearity (R2%) was (99.65). 

The method's detection limit (L.O.D.) of the new method was 272.5 ng/25 µL; it was calculated 

by diluting the minimum concentration in the calibration curve gradually. RSD% was less than 

0.2% for 0.9, 1.5, and 3.0 mmol/L concentrations of C.A.P. for n=8. The method was 

successfully applied to estimate C.A.P. in three pharmaceutical preparations, each produced by 

a different company. The new method was compared with the UV-Spectrophotometric method 

(classical method) at λmax= 207.2 nm by using the method of standard additions. Both the t-

test and the F-test were conducted to ensure that there wasn't a significant difference between 

the new method and the conventional one. The results of both tests showed, at a confidence 

level of 95%, that there was no significant difference. 

 

Keywords: Captopril, Flow injection analysis, Hypertension, Ayah 6S×1-ST-2D solar cell 

Continuous flow injection analyzer.  

Received 16 January 2023, Received 20 February 2023, Accepted 27 February 2023, Published 20 January 2024 

 

 

Fast New Method for Estimation of Captopril in Pure and Pharmaceutical 

Preparation by Reaction with Ammonium Ce (IV) Sulfate in Acid Medium 

 

doi.org/10.30526/37.1.3191 

https://creativecommons.org/licenses/by/4.0/
https://jih.uobaghdad.edu.iq/index.php/j/index#1609-4042
https://jih.uobaghdad.edu.iq/index.php/j/index#2521-3407
mailto:muntadhar.jabbar2105m@ihcoedu.uobaghdad.edu.iq
https://orcid.org/0000-0003-0023-9866
mailto:muntadhar.jabbar2105m@ihcoedu.uobaghdad.edu.iq
https://orcid.org/0009-0009-5781-4850
mailto:elham.n.m@ihcoedu.uobaghdad.edu.iq


IHJPAS. 37 (1) 2024 

266 
 

1. Introduction 

Arterial hypertension is one of the most prevalent diseases in the world [1,2] due to many factors, 

including those related to old age, family medical history, weight gain, stress, psychological stress, 

excessive salt intake, excessive drinking of alcohol, smoking In addition to other reasons [3,4]. 

This necessitated the search for effective medications to treat this disease; the first controlled 

therapy used in the treatment of arterial hypertension was captopril [5]. Pure captopril appears as 

a white crystalline powder with a slight sulfur odor [6], chemically named-[(2S)-3-mercapto-2-

methylpropionyl]-L-proline [7,8], its chemical formula C9H15NO3S (M.Wt=217.29 g/mol), the 

molecular structure of CAP is shown in Figure 1 [8,9], it dissolves easily in water and has 

solubility as well in methanol and ethanol [10].  

Captopril is a preferred treatment for many doctors due to its therapeutic benefits, efficacy, and 

low commercial price [11]. It’s mainly used for the treatment of arterial hypertension, heart failure 

[12-14], diabetic nephropathy [15], and some other diseases resulting from heart failure [16]; it’s 

widely used by geriatric patients who suffer from these diseases [17].  

Captopril may cause side effects such as coughing [18]. Captopril has been quantified by more 

than one analytical method, including spectrophotometry [19-22], flow injection methods [23-28], 

RP-HPLC [29,30], and HPLC [31-33].  

Some of these methods are not simple for routine analysis, requiring expensive or complex tools. 

Analytical systems by flow injection are more suitable for everyday use in quality control 

laboratories for the production of pharmaceutical preparations due to their simplicity of work, 

speed, sensitivity, and less consumption of reagents, sample samples, and other chemicals when 

compared to other methods of chemical analysis. This study describes a simple, sensitive, fast, 

low-contamination, easy-to-operate analytical method for determining CAP within the continuous 

flow injection analysis (CFIA) technique [34-40].  

Captopril was estimated after its interaction with ammonium by studying the precipitate formed 

as a result of the oxidation of CAP in an acidic medium using homemade Ayah 6SX1-ST-2D solar 

cell CFI analyzer [41], which was used in previous studies for the determination of some drugs 

[42-47]. 

 

 

 

2. Materials and Methods 

2.1 Reagents and chemicals 

In this study, all chemicals of the analytical class were used, and the preparation was done using 

distilled water as a solvent. A stock solution of Captopril (C9H15NO3S, M.Wt 217.29 g/mol, SDI, 

10 mmol/L) the preparation was done by dissolving 0.21729 g in 100 mL distilled water. A stock 

solution (20 mmol/L) of ammonium ceric sulfate 2(NH4)2SO4 Ce(SO4)2.31/2 H2O (M.Wt 659.62 

g/mol, Hopkin & Williams) preparation was done by dissolving 6.5962 g in 500 mL of distilled 

water. A 100 mmol/L from each of the following acids (supplied from BDH)  sulfuric acid solution 

Figure 1. Molecular structure of captopril 

 



IHJPAS. 37 (1) 2024 

267 
 

(98% w/w, 1.84 g/mL), hydrochloric acid solution (35% w/w, 1.19 g/ml), nitric acid solution (70% 

w/w, 1.42 g/mL), acetic acid solution (99.5% w/w, 1.05 g/mL). (100mmol/L) from each of the 

following salts (supplied from BDH): NaCl (M.Wt 58.44 g/mol, BDH), NaNO2(M.Wt 68.9953 

g/mol, BDH), NaNO3 (M.Wt 84.9947 g/mol, BDH), NH4Cl (M.Wt 53.491 g/mol, BDH), Na2CO3 

(M.Wt 105.99 g/mol, BDH).  

2.2 Sample preparation 

Twenty tablets of each pharmaceutical preparation were crushed using a ceramic mortar and sieved 

through a 200-mesh sieve. Each of the drugs containing (25 mg) CAP (provided by SDI-Iraq, 

Pioneer Pharmaceutical-Iraq, and Medochemi-Cyprus) weighed (1.2186, 0.9447, and 1.1612) g, 

respectively. According to the proportional relationship for each preparation, each of the weights 

above is equivalent to (0.21729 g) of the active substance to obtain a solution with a concentration 

of (10 mmol/L) of each pharmaceutical preparation. With continuous stirring, the powder was 

dissolved in distilled water. After the dissolution, the volume was completed to (100 mL) with 

distilled water. Then, the prepared solution was filtered to eliminate any undissolved material that 

may affect the result. 

2.3 Apparatus 

The apparatus used in the new method for CAP determination consists of a two-channel variable 

speed peristaltic pump (Supplied from Ismatec, Switzerland) and a six-hole medium-pressure 

injection valve (Supplied from IDEX corporation, U.S.A.) with a sample loop (0.7 mm i.d. Teflon, 

different length). Ayah 6S×1-T-2D Solar cell CFI analyzer (Homemade) The response was 

measured by it; three pairs (6) snow white LEDs are used as the beam source in the flow cell where 

the path length 2 mm, as a detector to collect signals via a 60 mm travel-sample, two solar cells 

were used. The response is output in the form of peaks through the x-t potentiometric recorder 

(Kompenso Graph C-1032, supplied from Siemens-Germany) (1-500 volt, 1-500 mV), the flow 

diagram for the determination of CAP is shown in Figure 2. For measurements, the UV-

Spectrophotometric method used a UV-Vis spectrophotometer (Shimadzu double beam. In this 

device, the wavelength scanning range was 190-1100 nm, and the 1 mL measuring cell was made 

of quartz, model UV-1800 Kyoto-Japan). 

 

 

 

 

 

 

 

 

 

 

 

  

 

Two lines make up the manifold flow system in Figure 2 for determining CAP by direct oxidation 

in an acidic medium with ACS, where a slightly yellowish precipitate was formed. The first line 

provided nitric acid (200 mmol/L), which is a carrier stream at (1.5 mL/min) connected to the 

injection valve for hold CAP (used sample volume 25 µL), the second line carried ACS                           

Figure 2. Flow diagram for the system used to determine captopril 



IHJPAS. 37 (1) 2024 

268 
 

(10 mmol/L) at 1.5 mL/min. The second line meets the first line (which the CAP solution is 

injected into) at the Y-Junction, and reaction products outlet from it to pass through the Ayah 

6S×1-ST-2D Solar cell CFI analyzer. Each solution was injected three times in succession. An x-

t potentiometric recorder was used to capture the response diagram, where the responses appeared 

in the form of peaks expressing the transducer's response and the peak height representing the 

amount of light reflected after it fell on the surface of the sediment particles in the flow cell. A 

proposed CAP oxidation mechanism by ACS in an acidic reaction medium is present in Sketch 1 

[16,17,48].  

 

 

 

3. Results and Discussion 

The concentration of the ACS reagent, the selection of the type of reaction medium (carrier 

stream), and the concentration of the optimal medium (nitric acid) were mainly studied to 

determine some of the optimal chemical parameters. Meanwhile, the flow rate and sample volume 

were studied to resolve some optimal physical parameters. By making it constant and variable each 

time these variables were optimized. 

3.1 Chemical variables  

3.1.1 Effect of ACS concentration 

A series of concentrations of ACS (1-20) mmol/L was prepared. A 2 mmol/L of CAP was injected 

using a sample volume of 25µl and distilled water as carrier stream; 2.3 ml/min was the flow rate 

for each of the reagent lines and carrier streamline. All measurement was refined three times. The 

response outline for this experience is shown in Figure 3A, and Figure 3B shows the effect of 

ACS concentration on the peak rise average of the response’s transducer. The results were 

compacted in Table 1. The results found that the highest response appeared at the concentration 

of (10 mmol/L), so it was determined as an optimal concentration of the reagent. Figure 3 shows 

the outline of the result using Ayah 6S×1-ST-2D Solar cell-CFI analyzer; the responses of white 

precipitate increase ascendingly with a rise in concentration of ACS until reaching a concentration 

of 10 mmol/L, then the reaction begins to gradually decrease after this concentration (˃ 10 

mmol/L) of ACS; this may be attributed to increasing in the amount of sediment, which causes 

slow movement of its particles and an increase in the aggregation of those particles, mainly causing 

accumulation of precipitate particles in front of the detector which in turn to a decrease in reflecting 

surface, this results in a reduction of peak height.  

From Figure 3A, it is clear that the peak of response was higher and the width of the baseless, so 

the concentration of 10 mmol/L was chosen for the subsequent experiments as the optimal 

concentration of the reagent (ACS). Figure 3B shows ACS concentrations on the transducer 

response peak rise rate in (mV). 

 

Sketch 1. The suggested mechanism of the CAP and ACS reaction in acidic medium  



IHJPAS. 37 (1) 2024 

269 
 

 

 

 

 

 

 

 

 

 

 

 

 

 Table1. Synopsis of the results of effect of the concentration of ACS reagent on the responses average of the transducer 

 

 

 

 

 

3.1.2 Effect of different medium  

 To determine the optimal reaction medium between CAP (2 mmol/L) with ACS (10 mmol/L), 

different solutions were used as carrier current (CH3COOH, HCl, HNO3, H2SO4, NaCl, NH4Cl, 

NaNO2, NaNO3, Na2CO3). At a concentration of 0.1 mol/L and in the aqueous medium. It was 

observed in the study that the response plot over time in this experiment showed variation in the 

intensity of the S/N response (variation in the height of the peaks). The plot also showed that the 

highest response was when nitric acid was used as the reaction medium (carrier current). This may 

be due to the small and uniform size of the deposited particles, in other words, the increased 

reflective surface area. Therefore, the medium HNO3 solution was used as the carrier current in 

the following experiments. The responses that demonstrated this are shown in Figure 5A.  

Figure 5B Schematic showing the effect of medium change on the average response of the 

transducer. Table 2 summarizes the results of the impact of the type of medium. 

 

 

 

 

 

[ACS] mmol/L Response average 

�̅�𝐢(mV)for (n=3) 

R S D % Interval of confidence at (95%),n-1 

�̅�i±t0.05/2,n-1
𝝈𝒏−𝟏

√𝒏
 

1 8 0.2051 8 ∓ 0.0407 

3 52 0.2001 52 ∓ 0.2586 

5 100 0.2212 100 ∓ 0.5495 

8 112 0.2301 112 ∓ 0.6402 

10 184 0.2312 184 ∓ 1.0568 

13 160 0.2340 160 ∓ 0.9301 

15 144 0.2190 144 ∓ 0.7834 

20 128 0.2132 128 ∓ 0.6779 

Figure 3. ACS concentration’s effect on : A: response outline versus time. B: Peak rise rate of transducer response in (mV) 

 

[ACS] mmol/L 

R
e
sp

o
n

se
 a

v
e
r
a
g
e𝐘

𝐢(
𝐦

𝐕
) 

(n
=

3
) 

Optimum conc. of 

ACS 

0 5 10 15 20

0

20

40

60

80

100

120

140

160

180

200

(B) 

 Y̅i(mV)(S/N) response of an energy transducer in (mV) for n=3,ttab0.05/2,2=4.303.R.S.D%:relative standard deviation, 
σn-1:standard deviation, n: the number of repetitions of the measurement, Interval of confidence: A range of values 

above and below the point estimate within which the true value in the population is likely to lie with 95%. 

t(min)d(cm) 

Y
 (
m

V
) 

(A) 
[ACS] mmol/L 



IHJPAS. 37 (1) 2024 

270 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2. A synopsis of the effects of several medium types on the transducer's average responses 

 

3.1.3 Effect of HNO3 concentration 

Using CAP (2 mmol/L)-ACS(10 mmol/L) system within the range (20-240 mmol/L) a series of 

solutions of nitric acid were prepared; the sample volume was (25 µL) at a flow rate (of 1.5 

mL/min) for both of the first lines (carrier stream) with the second line (reagent). Figure 4A shows 

the effect of HNO3 concentration on the responses in the response outline, and Figure 4B shows 

the effect of HNO3 concentration change on the peak rise rate of the transducer response. 

Experiment results are compacted in Table 2. It was observed through the increased intensity of 

the reactions shown in Figure 5A. (20 mmol/L) from HNO3 it was the first solution to be 

measured, and what is observed in Figure 5B is that the response increases by increasing the 

concentration until reaching concentration (200 mmol/L), which indicates that the acid was 

necessary because of its effect stimulating the reaction, the complete dissolution of the ACS salt 

and to ensure complete homogeneity. The concentration (200 mmol/L) gave the peak's highest 

response and the lowest width. Therefore, the concentration (200 mmol/L) of HNO3 was selected 

as the optimal concentration for the optimum carrier stream in the subsequent experiments. 

 

  

[Medium type] 

mmol/L 

Response average  

�̅�i(mV)for (n=3) 

 

R S D % 

Interval of confidence at 

(95%),n-1 

�̅�i±t0.05/2,n-1
𝝈𝒏−𝟏

√𝒏
 

H2O 184 0.2312 184 ∓ 1.0568 

CH3COOH 100 0.2100 100 ∓ 0.5217 

HCl 384 0.2200 384 ∓ 2.0987  

HNO3 476 0.2016 476 ∓ 2.3849 

H2SO4 104 0.2001 104 ∓ 0.51699 

NaCl 108 0.2200 108 ∓ 0.5903 

Na2CO3 16 0.2100 16 ∓ 0.0835 

NaNO3 108 0.2100 108 ∓ 0.5680 

NaNO2 20 0.2000 20 ∓ 0.0994 

NH4Cl 108 0.2201 108 ∓ 0.5905 

(B) 
The optimum 

medium 

R
e
sp

o
n

se
 a

v
e
r
a
g
e𝐘

𝐢(
𝐦

𝐕
) 

(n
=

3
) 

(A) 

Figure 4A. Response outline versus time explain the effect of different media. B:A graphical diagram showing the 

effect of medium change on the response average of a transducer 



IHJPAS. 37 (1) 2024 

271 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3. Synopsis of the results of responses to effect of HNO3 concentration on the responses average of the 

transducer 

 

3.2 Physical variables 

3.2.1 Flow rate  

The optimal flow rate was studied within the range (1.0- 2.5) mL/min for both line (carrier 

streamline) and line 2 (reagent line); a peristaltic pump was used to control the flow rate for 

determination of CAP at (2 mmol/L). The study was carried out by fixing the other parameters 

(i.e., 10 mmol/L from ACS, 0.2 mmol/L from HNO3 as the best carrier stream, sample volume 

was 25 µL, and open valve (10 sec). The results of the experiment were compacted in Table 4. A 

slow flow rate (1 mL/min) was shown to generate an increase in dilution and dispersion, which 

may have led to the rise in the base width of the response ∆tB, While the flow rates higher than 

(1.5 mL/min) showed a gradual decrease in the response with irregularity in the peaks of some 

responses, this may be attributed to the fact that at high speed the sample retention time with the 

detector is reduced. It is the least possible. This leads to a decrease in the amount of light reflected 

towards the sensor, which reduces the intensity of the response. Figure 6A shows a plot of the 

transducer response against time. Figure 6B shows the effect of changing flow rate on the rate of 

peak rise of the transducer response, base width, and arrival time to the measuring flow cell. It was 

found from the two charts that the highest response was recorded at the pump speed 10                   

(1.5 mL/min), so it was chosen as the optimal speed in the subsequent experiments.  

 

 

 

 

[HNO3] mmol/L 
Response average 

 �̅�𝐢(mV)for (n=3)  
R S D % 

Interval of confidence at (95%),n-1 

�̅�i∓t0.05/2σn-1/√𝐧 

20 68 0.2941 68 ∓0.4968 

60 292 0.2911 292 ∓ 2.1116 

100 476 0.2016 476 ∓ 2.3849 

140 496 0.1411 496 ∓ 1.7390 

200 696 0.1408 696 ∓ 2.4346 

240 500 0.1760 500 ∓ 2.1862 

Figure 5. HNO3 concentration's effect on: A: response shape against time . B: Peak rise rate of transducer response in (mV) 

 

 

(B) 

R
e
sp

o
n

se
 a

v
e
r
a
g
e𝐘

𝐢(
𝐦

𝐕
) 

(n
=

3
) 

0 50 100 150 200 250

0

100

200

300

400

500

600

700

[HNO3] mmol/L 

Optimum 

conc. of HNO3 

(A) 

Y
(m

V
) 

t (min) d (cm) 



IHJPAS. 37 (1) 2024 

272 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 4. An synopsis of the findings showing how changing flow rate affected the transducers' average responses 

 

pump 

speed 

Flow rate  

(ml/min) 

both two 

lines 

Response 

average 

�̅�i(mV) 

 (n=3) 

 

 

R S D% 

Interval of 

confidence at 

95% 

�̅�i±t0.05/2.
𝝈𝒏−𝟏

√𝒏
 

  

 

t 

(sec) 

Base 

width 

∆tB 

(sec) 

Vadd 

(ml) 

In flow 

cell 

Conc.  

(mmol/L) 

In flow 

cell  

 

 

Df 

5 1.0 2000  0.1050 2000∓ 5.2171 66 162 5.4250 0.0092 217.3913 

10 1.5 1620 0.1111 1620 ∓ 4.4718 18 90 4.5250 0.0110 181.8181 

15 1.8 1340 0.1044 1340 ∓ 3.4780 15 72 4.3450 0.0115 173.9130 

20 2.0 920 0.1195 920 ∓ 2.7327 12 54 3.6250 0.0138 144.9257 

25 2.3 696 0.1408 696 ∓ 2.4346 9 42 3.2450 0.0154 129.8701 

30 2.5 240 0.1041 240 ∓ 0.6210 6 36 3.0250 0.0165 121.2121 

 

 

3.2.2 Sample volume  

With the use of optimum flow rate (1.5 mL/min) for both the carrier stream with ACS reagent line, 

CAP (2 mmol/L)-ACS (10 mmol/L)-HNO3 (200 mmol/L) system. Various volumes of injected 

sample were used within the range (20-100) µL, open valve 10 sec. It was observed through the 

transducer's responses outline against time there was an apparent increase in the intensity of the 

reaction at sample volume 25 µL, as shown in Figure 7A, B where the highest peak appeared. A 

synopsis of the results of the experiment is shown in Table 5. Increasing the sample volume (to 

more than 25 µL) might lengthen the sample piece's exposure to the detector. This would likely 

result in an irregular flow of two factors, dispersion, and convection, allowing the convective 

current to continue and causing the precipitating particles to migrate backward. If the reflective 

surface weren't damaged somehow, it would still be able to reflect the light from the incident 

source. According to this potential explanation, the response peak height would be smaller, and 

the peak profile would be broad. Figure 7A shows a plot of the transducer response against time. 

At the same time, Figure 7B shows the effect of changing sample volume on the rate of peak rise 

of the transducer response, base width, and arrival time to the measuring flow cell. It was found 

from the two charts that the highest response was recorded at the sample volume of 25 µL, so it 

was chosen as the optimal sample volume in the subsequent experiments. 

Figure 6. Flow rate’s effect on: A: response outline against time . B: Peak rise rate of transducer response in (mV) 
and base width 

 

(A) (B) 

t: Time arrival estimated from the injection valve to the measurement cell (sec),∆t: Base width of peak(sec), Vadd: 

Addition volume(ml)in flow cell, Df: Dilution factor in flow cell. 



IHJPAS. 37 (1) 2024 

273 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 5. Synopsis of the results of the effect of the difference in the sample volume on the average of transducer’s responses 

Sample 

volume

(µl) 

 

Response 

average  

�̅�i(mV) 

 (n=3) 

 

 

R S D % 

Interval of 

confidence at 

(95%), n-1 

�̅�i±t0.05/2.
𝝈𝒏−𝟏

√𝒏
 

 

t 

(Sec) 

Base 

width 

∆tB 

(Sec) 

Vadd 

(ml) 

In flow 

cell  

Conc. 

(mmol/L) 

In flow cell  

 

 

Df 

20 920 0.1108 920 ∓ 2.5340 12 84 4.4000 0.0090 222.222 

25 1620 0.1111 1620 ∓ 4.4718 18 90 4.5250 0.0110 181.8181 

50 1440 0.1138 1440 ∓ 4.0743 21 93 4.7000 0.0212 94.3369 

75 1420 0.1140 1420 ∓ 4.0246 27 105 5.3250 0.0281 71.1743 

100 1300 0.1230 1300 ∓ 3.9749 30 120 6.1000 0.0327 61.1620 

 

 

 

3.3 Calibration curve (scatter plot) for variance of CAP concentration against transducer 

response  

The optimal chemical and physical parameters were adopted to prepare a series of CAP solutions 

within the range (0.07-10) mmol/L, the measurement was repeated for each concentration three 

successive times. Responses are shown as in Figure 8A which shows the response range and peak 

height for each concentration of CAP. As shown in Figure 8B the linear calibration was within 

the range (0.07-3) mmol/L, accompanied by a correlation coefficient (r)= 0.9983. The obtained 

results show the linear regression of the change of transducer response against the change of CAP 

concentration as in Table 6, the equation that was used in this part of the study was ŷ = a + bx 

[49] (First degree equation). The value of t was calculated at a confidence level (95%) , which was 

greater than the value of the tabular t, which leads us to say that linearity versus nonlinearity is 

acceptable.  

 

 

 

 

 

 

(A) 

A
r
r
iv

a
l 

ti
m

e 
to

 t
h

e 

m
e
a
su

r
in

g
 f

lo
w

 c
el

l 
(s

ec
) 

B
a
se

 w
id

th
 ∆

tB
 

(s
e
c
) 

20 40 60 80 100

900

1000

1100

1200

1300

1400

1500

1600

1700

Response average (mV)

Base width ∆tB (sec)

Arrival time to the measuring flow cell (sec)

80

85

90

95

100

105

110

115

120

125

10

12

14

16

18

20

22

24

26

28

30

32

R
e
sp

o
n

se
 a

v
e
r
a
g
e𝐘

ത
𝐢(

𝐦
𝐕

) 

(n
=

3
) 

Sample volume (µl) 

(B) 

t: Time arrival estimated from the injection valve to the measurement cell (sec), ∆t: Base breadth of peak(sec), 

Vadd: Addition volume(ml)in flow cell, Df: Dilution factor in flow cell. 

Figure 7. Sample volume’s effect on: A:Outline’s response against time . B: Peak rise rate of transducer 

response in (mV) and base breadth 

 



IHJPAS. 37 (1) 2024 

274 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
Table 6. Synopsis of results the transducer response average against changing CAP concentration using first degree 

equation 

 

 

 

3.4 Limit of detection (L.O.D)  

The method's detection limit is the minimum concentration that the device can sense. A study 

determined the CAP detection limit through three methods: practically based on diluting to the 

minimum concentration gradually, theoretically based on the slope value, use, and on the base of 

the linear equation, as shown in Table 7 at optimum parameters. 

 

 

 

 

Type of 

mode 

Range of 

[CAP]  

mmol/L 

 

 

𝐘(mV) =a ±Sa.t+b±Sb.t[CAP]mmol/L at 95%.n-2 

r 

r2 

R2% 

ttab at 

95%, 

n-2 

 

tcal=
|𝐫|√𝒏−𝟐 

√ 𝟏−𝐫 𝟐
 

Scatter 

plot 

0.07-10 

(n=19) 

 

629.1921±310.3027 + 243.3006 ± 93.4715[CAP] 

0.7996 

0.6395 

63.95 

 

2.110<5.4910 

Linear 

range 

0.07-3 

(n=16) 

 

45.8635±37.3236+748.8995±25.0941[CAP] 

0.9983 

0.9966 

99.66 

 

2.145<<63.1962 

Figure 8A. A calibration curve shows the effect of CAP concentration change against time on 

transducer response (for some responses) 

Figure 8B. Scatter and linear plot of the new method expresses the transducer response against conc. by linear equation 

n:number of measurement ,Ŷ(mV):estimated value of cell in(mV) , r:Correlation coefficient, r2:Coefficient of 

determination, R2%:Explained variation as a percentage / total variation, ttab=t0.05/2,n-2 

(A) 

 𝐘
𝐢(

𝐦
𝐕

)(
 n

=
3

) 

 s
u

cc
es

si
v
e
 m

ea
su

re
m

en
ts

 

(B) 



IHJPAS. 37 (1) 2024 

275 
 

Table 7. Method’s detection limit value for CAP 

Practically based on the progressive 

dilution for the minimal 

concentration (0.07)mmol/L  

Theoretical in accordance with the 

slope value X=3SB/Slope , n=16  

Based of linear equation 

𝐘=Yb + 3Sb 

272.5 ng /25µL 6.5277 ng /25µL 877.5 ng /25µL 

 

 

3.5 Repeatability 

Equivalent percentage equivalent to the test-retest measurement reliability expresses the relative 

standard deviation. The responses were re-measured for each concentration through eight 

consecutive injections for three stable CAP concentrations (0.9, 1.5, and 3.0) mmol/L in optimum 

conditions for n=8. The response profile is shown in Figure 9. Table 8 displays that the relative 

standard deviation as a percentage was less than 0.2%, making it abundantly evident that the 

suggested approach and instrument were suitable for determining CAP. 

 

 

 

 

 

 

 

 

 

 

 

Table 8. Synopsis of results for repeatability of CAP at optimal parameters  

 

 

 

 

 

 

 

3.6 UV-Spectrophotometric method (Classical method)  

To evaluate the new method (CFIA), a comparison was made between it and one of the analytical 

methods, specifically the UV spectrophotometry method based on absorption value measurements. 

The concentration extent of the method was (0.002-0.150) mmol/L at λmax= 207.2 nm (at 0.028 

mmol/L) Figure 10 using quartz cell. Figure 11 shows the scatter plot was from (0.002-0.150) 

mmol/L while the linear range was (0.002-0.09) mmol/L. Correlation coefficient (r)= 0.9995 and 

R2%=99.90, n=18 (n= number of measurements). L.O.D. was 217.29 ng/1000 μL, calculated by 

gradual dilution to the lowest concentration in the calibration curve (0.002 mmol/L). The summary 

of the method results is in Table 9. 

 

 

 

[CAP] 

mmol/L 

Response average  

�̅�i(mV)for (n=8)  

 

R S D % 

Interval of confidence at 95% 

�̅�i±t0.05/2,n-1.
𝝈𝒏−𝟏

√𝒏
 

0.9 760 0.1052 760± 0.6689 

1.5 1140 0.1052 1140 ± 1.0033 

3.0 2240 0.1026 2240 ±1.9231 

X= limit of detection value , SB=standard deviation value of blank refined for 16 times, Yb: average response for  

blank=intercept(a), Sb: Standard deviation equal to Sy/x(residual) from linear range ,Ŷ:estimated response (mV). 

 

Figure 9. Response versus time outline for eight consecutive repeated measurements of CAP concentration 

(0.9,1.5,3.0) mmol/L  

ttab0.05/2,7=2.365, n: the number of repetitions of the measurement 



IHJPAS. 37 (1) 2024 

276 
 

 

 

 

 

 

 

 

 

 

 

 

 

Table 9. Synopsis of linear regression for the determination of CAP using UV-Spectrophotometric method (classical 

method) 

 

 n:number of measurement ,Ŷ(mV):estimated value without unite on spectrophotometric , r:Correlation coefficient, 

r2:Coefficient of determination, R2%:Explained variation as a percentage / total variation, ttab=t0.05/2,n-2, L.O.D.: Limit 

of detection. 

 

3.7 The CAP-ACS-HNO3 system evaluation for the CFIA method (new method) for 

determining captopril in pharmaceutical preparations 

To evaluate the efficiency of the new method, which was made using Ayah 6S×1-ST-2D Solar 

cell CFI analyzer (homemade), to determine CAP in pharmaceutical preparations. Five solutions 

were prepared for each drug for samples from three different companies for the production of 

pharmaceutical preparations (SDI-Iraq, Pioneer-Iraq, and Medochemi-Cyprus), where comparison 

was made with the UV-Spectrophotometric method(classical method) after applying the method 

of standard additions to both the two methods are as follows: 

For the new method: five volumetric flasks of (10 mL) were prepared and (1.0 mL from 10 

mmol/L) was transferred into each of them, after which different volumes of the captopril’s 

standard solution were gradually added (S.D.I.-Iraq) (0.0, 0.5, 1.0, 1.5, 2.0) mL of (10 mmol/L) to 

gain (0.0, 0.5, 1.0, 1.5, 2.0) mmol/L. 

For the classical method: five volumetric flask of (10 mL) were prepared and (0.5 mL from 1.0 

mmol/L) was transferred into each of them, after which different volumes of captopril’s standard 

solution were gradually added (S.D.I.-Iraq) (0.0, 0.1, 0.2, 0.3, 0.4) mL of (1.0 mmol/L) to gain 

(0.0, 0.01, 0.02, 0.03, 0.04) mmol/L. Flask number 1 is a sample. Measurements were made for 

both methods. The results obtained from the standard addition method were treated statistically. 

The results are summarized in Table 10A and B at a confidence level (95%). To determine whether 

Type 

of 

mode 

Extent in 

calibration 

curve  

 

n 

linear regressive at Interval of 

confidence 95%,n-2 

𝐘=a±Sa.t+b(∆y/∆xmmol/L)±bt 

[CAP]mmol/L 

r  

r2 

R2% 

ttab at 95% ,n-

2 
tcal=

|𝐫|√𝒏−𝟐

√𝟏−𝐫𝟐
 

 

 

L.O.D. 

 

Scatter 

plot 

 

0.002-0.150 

 

22 

 

0.0639±0.0750+4.5582±1.1779[CAP] 

0.8746 

0.7650 

76.50 

 

2.086<8.0695 

Linear 

plot 

 

0.002-0.09 

 

18 

 

0.0052±0.0048 +6.6818±0.1185[CAP] 

0.9995 

0.9990 

99.90 

 

2.120 << 126.5189 

217.29 ng/1000µ 

Figure 11. Scatter plot at (0.002-0.15) mmol/L, n=22 for CAP using classical method at 

207.2 nm, in addition to linear range at (0.002-0.09)mmol/L for n=18 

 

Figure11. Scatter plot at (0.002-0.15)mmol/L, n=22 for CAP using classical method at 

207.2 nm, in addition to linear range at (0.002-0.09)mmol/L for n=18. 

Figure 10. Absorbance of UV-Spectrum of 

CAP at concentration 0.028 mmol/L that 

shows λmax=207.2 nm 

 

Type 

of 

mode 

Extent in 

calibration 

curve  

 

n 

linear regressive at Interval of 

confidence 95%,n-2 

𝐘=a±Sa.t+b(∆y/∆xmmol/L)±bt 

[CAP]mmol/L 

r  

r2 

R2% 

ttab at 95% 

,n-2 
tcal=

|𝐫|√𝒏−𝟐

√𝟏−𝐫𝟐
 

 

 

L.O.D. 

 

Scatter 

plot 

 

0.002-0.150 

 

22 

 

0.0639±0.0750+4.5582±1.1779[CAP] 

0.8746 

0.7650 

76.50 

 

2.086<8.0695 

Linear 

plot 

 

0.002-0.09 

 

18 

 

0.0052±0.0048 +6.6818±0.1185[CAP] 

0.9995 

0.9990 

99.90 

 

2.120 << 126.5189 

217.29 ng/1000µ 

 concentration 0.028 mmol/L that shows 

λmax=207.2nm 



IHJPAS. 37 (1) 2024 

277 
 

there is a significant difference, the t-test and the F-test were performed, and the results were 

processed statistically [49]. The results of the t-test and F-test were summarized in Table 10B 

(columns 4 and 5). Results showed there was no significant difference between the new method 

and the classical method at 95% of the level of confidence. A t-calculated (-1.373) is less than the 

t-tabular (4.303), as well as the calculated F-value (8.7064) is less than the tabular F-value (39) 

[50]. Figure 12 is a graphical chart showing how changing the CAP concentration (using the 

standard addition method) affects the S/N transducer’s response against time. 

 

 

 

 

 

 

 

 

 

 

 

 

Table 10A. Synopsis of results standard addition in three pharmaceutical preparations for new method and classical method. 

Ŷ: Estimated response in (mV) for the new method and the UV-Sp.method absorbance value, r: correlation coefficient, R2%: variance 

explained in percentage /total variation, UV-Sp. :UV-Spectrophotometric method, ѿi : Practical weight in( mg), ttab= t0.05/2,∞ =1.960 at 

95%,ttab= t0.05/2,3= 3.182 for n=5,using volume of cell (quartz) 1 mL in UV-Spectrophotometric method. 

 

N
o
. 
o
f 

sa
m

p
le

 
          

 

C
o

m
m

er
ci

al
 n

am
e 

C
o

m
p

an
y
 

C
o

n
te

n
t 

C
o

u
n

tr
y
 

            

Type of method 

New method 

UV-Sp. Method absorbance measurements at λmax= 207.2 nm 

Confidence 

interval 

for the  

Weight of 

Tablet 

ѿ i ± 

1.96σn-1/√n 

at 95% 

(g) 

Weight of 

the 

sample is 

equivalent 

to 

0.21729 

(g) 

(10 

mmol /L) 

of 

 the active 

ingredient 

Wi (g) 

Theoretical 

content for 

the active 

ingredient at 

95% 

(mg) 

Wi ±1.96σn-

1/√n 

Captopril  

Standard addition equation at 95% for n-2 

 

 

 

 

 

 

 

 

 

r 

 

r2 

 

R2% 

 

0 

mL 

 

0.5 

mL 

 

1.0 

mL 

 

1.5 

mL 

 

2.0  

mL 

  

 

Ŷ (mV) =a mV ±Sa.t+ b(Δ y mV /Δxmmol/)b.t 

[Captopril]mmol/L 

 

 

 

  

 

0 

mmol

/L 

 

0.5 

mmol

/L  

 

1.0  

mmol

/L 

 

1.5  

mmol

/L 

 

2.0 

mmol

/L  

 

0 

mL 

 

0.1 

mL 

 

0.2 

mL 

 

0.3 

mL 

 

0.4  

mL 

 

 

Ŷ =a± Sa.t +b (Δ y / Δx mmol/L )±Sb .t 

[Captopril] mmol/L  

0 

mmol

/L 

 

0.01 

mmol

/L 

 

0.02 

mmol

/L 

 

0.03 

mmol

/L 

 

0.04 

mmol

/L 

 

 

 

1 

C
ap

to
sa

m
 

S
.D

.I
 

2
5

 m
g
 

Ir
aq

 

 

 

 

0.14021±0.0

010 

 

 

 

1.2186 

 

 

 

25±0.1930 

 

790 

mV 

 

1100 

mV 

 

1590 

mV 

 

1910 

mV 

 

2230 

mV 

 

752 ±66.5941+758±54.3740[ CAP]mmol/L  

0.9992 

0.9984 

99.84 

 

0.342 

 

0.412 

 

0.478 

 

0.540 

 

0.613 

 

0.343 ±0.0070+6.700±0.2959 [CAP]mmol/L 

0.9996 

0.9994 

99.94 

 

 

 

2 

C
ap

to
n

ee
r 

P
io

n
ee

r 

2
5

 m
g
 

Ir
aq

 

 

 

0.1087±0.00

07 

 

 

 

0.9447 

 

 

 

25±0.1769 

 

750 

mV 

 

1050 

mV 

 

1550 

mV 

 

1900 

mV 

 

2220 

mV 

 

736±137.3058+758±112.1098 [ CAP ]mmol/L 

0.9967 

0.9935 

99.35 

 

0.324 

 

0.401 

 

0.450 

 

0.520 

 

0.602 

 

0.3244±0.0235+6.7500±0.9660[ CAP ]mmol/L 

0.9969 

0.9939 

99.39 

 

 

 

 

3 

 

R
il

ca
p

to
o
 

L
im

as
so

l 

2
5

 m
g
 

C
y

p
ru

s(
E

U
) 

 

 

0.1336±0.00

03 

 

 

 

1.1612 

 

 

 

25±0.06831 

 

780 

mV 

 

1110 

mV 

 

1585 

mV 

 

1915 

mV 

 

2235 

mV 

 

760±70.6874+761±57.7160 [CAP]mmol/L 

0.9991 

0.9982 

99.82 

 

0.360 

 

0.440 

 

0.501 

 

0.570 

 

0.645 

 

0.3632±0.0120+7.0000±0.5024 CAP ]mmol/L 

0.9991 

0.9984 

99.84 

Figure 12. Effect of variation of captopril concentration (using standard addition method) on S/N energy transducer response 

versus time(min),distains (cm) for three sample drugs using Ayah 6S×1-ST-2D solar cell CFI analyser . 1-Iraq, Captosam, S.D.I., 

2-Iraq, Captoneer, Pioneer, 3-Cyprus, Rilcaptoo. Limassol 



IHJPAS. 37 (1) 2024 

278 
 

Table 10B. Synopsis of practical content results ,percentage recovery (Rec.%) for CAP determination in three pharmaceutical 

preparations, t-test and F-test 

X̅d : Comparing two types of methods, on average (new & classical) ,n(no. of sample)=3,σn-1:standard deviation of different 

(paired t-test), ttab=t0.05/2,2=4.303 (for paired t-test), Ftab= F 0.95,V1,V2= F 0.95,2,2=39, σ**n-1 : standard deviation for new method, 

σ*n-1 standard deviation for classical method ( F-test),S2
1(CFIA):Variation of new method, S2

2(UV-Sp.):Variation of classical 

method. UV–Sp.: UV–Spectrophotometric method . 

4. Conclusion 

The method presented in this work is simple, sensitive, fast and meets part of the requirements of 

green chemistry. It has been successfully applied for the determination of CAP in pure and 

pharmaceutical preparations based on the reaction of CAP with ACS in acidic media. An 

alternative analytical method for estimating CAP was reached through this study, which was 

conducted under simple conditions and parameters using Ayah 6SX1-ST-2D solar cell CFI 

analyzer . 

Acknowledgment 

After the completion of the study, the authors extend their thanks and appreciation to (S.D.I.) for 

providing the pure sample of the drug for free to the Department of Chemistry in the College of 

Science/ University of Baghdad to facilitate the task of completing some of the research 

requirements and to Prof.Dr. Issam M. Ali Al-Hashemi for his distinguished scientific effort in 

designing the Ayah 6SX1-ST-2D solar cell CFI analyzer, by which the work methodology in this 

study was completed. 

Conflict of Interest  

The authors declare that they have no conflicts of interest. 

Funding: None  

 

 

 

 

 
 
 

 

No. of 

sample 

Type of method  t-test  F-test  

New method  

 

 

 

tcal= 
�̅�𝒅

𝝈𝒏−𝟏
√𝒏 

 

 

 

 

ttab at level 

of 

confidence 

95%  

 

 

 

 

Fcal = S2
2/S

2
1 

 

 

 

 

Ftab 

UV-Sp. Classical method 

Absorbance measurement at 207.2 

nm 

Workable 

concentration 

(mmol/L) 

In 10 mL 

---------------- 

In 100 mL 

Efficiency of 

determination 

Rec.% 

 
 
 

1 

0.9920 
---------------- 

9.9200 

 
99.1728 

 
 
 

X̅d= - 0.5510 
σn-1=0.6953 
|-1.373| < 4.303 

 

 
 
 

σ** n-1=0.3546 , S1
2
(CFIA) =0.1257 

σ* n-1=1.0461 , S2
2
(UV-Sp.)=1.0944 

  
8.7064 < 39.0000 

 0.0514 

------------- 
10.286 

 

102.84 

 
 
 

2 

0.9709 
------------------ 

9.7097 

 
97.1039 

0.0480 
------------ 

9.6100 

 
96.1006 

 
 
 

3 

0.9986 
------------------ 

9.9860 

 
99.8200 

0.0518 
--------------- 

10.377 

 
103.7688 



IHJPAS. 37 (1) 2024 

279 
 

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