Indirect Electrochemical Determination of Chlorpropamide Through Its Interaction with Valsartan Using Square Wave Voltammetry


Amer Th. Al-Taee1*, Aws Z. Al-Hafidh2

1Department of Chemistry, College of Sciences, Mosul University, Mosul, Iraq.

2Chemical Industries, Technical Institute, Mosul, Northern Technical University, Mosul, Iraq.

*Corresponding Author E-mail:,



A square wave voltammetric technique coupled with three electrode detection system consist of hanging mercury drop electrode (HMDE) as working electrode, 1mm platinum wire as an auxiliary electrode (Pt-wire) and silver/silver chloride saturated potassium chloride (Ag/AgCl.sat.KCl) as reference electrode was used to determine the chlorpropamide indirectly through its interaction with valsartan, chlorpropamide gives no reduction peaks in the studied range. The effect of pH and the stability of the measurement were examined calibrations curve of chlorpropamide was constructed and the relation between current and concentration of chlorpropamide was linear with R2 value = 0.9944. The limit of detection for chlorpropamide was 4.89 x 10-9 M through its interaction with valsartan.


KEYWORDS: Chlorpropamide, Valsartan, Interaction, Square Wave Voltammetry.




Chlorpropamide 1-[(p-chlorophenyl)sulfonyl]-3-propylurea (Fig. 1). It is a drug in the sulfonylurea class used to treat diabetes mellitus type two1. Its mechanism of action involves the stimulation of insulin release from the β-cells of the pancreas in response to a glucose load2.


Fig. 1: Chemical structure of Chlorpropamide


The chlorpropamide was determination by several methods including high performance liquid chromatography (HPLC)3,4,5. A spectrophotometric method is used by British Pharmacopeia6, Spectrophotometric7, titrimetric8, thin layer chromatography9,10, gas chromatography11,12.



Charge-transfer complexes are formed by the interaction between electron donors and electron acceptors13.


Valsartan is chemically N-(1-Oxopentyl)-N-[[2'-(1H-tetrazol5-yl) [1, 1'-biphenyl]-4-yl] methyl]-L-valine (Fig. 2), it is an angiotensin receptor blocker, has been widely used for the treatment of hypertension14.


Fig. 2: Chemical structure of Valsartan


Several methods used to determination of valsartan such as UV–Spectrophotometric15, Liquid Chromatography-Mass Spectrometry16, High Performance Liquid Chromatography with Fluorescence Detection17, High Performance Thin Layer Chromatographic18.


Electrochemical methods used to study behaviour of many materials19,20, mercury electrode have been studied electrochemical behaviour for other materials21,22 and the interactions studied by electrochemical methods on dropping mercury electrode23.


Indirect determination of drugs is preferable because most of them free from interference so in this work we tried to determine chlorpropamide indirectly by its interaction with valsartan, this interaction can be synergistic through the increase or enhance the activity of drug, so the interaction can leads to overdose effect if patient take more than one drug and one of them increase the effect of the others. In the other hand if one drug decrease the activity of the other drug it may cause to have any therapeutic use because of under dosage24,25,26.


In our previous work, valsartan gives stable well-defined reduction peak at (-1.07) V versus Ag/AgCl.sat.KCl on HMDE working electrode in phosphate buffer (pH=7.0) supporting electrolyte27.



Chemicals and reagents:

All chemicals used were analytical grade (Fluka, BDH) and used without purification. The pure chlorpropamide and valsartan were kindly supplied by Sammira drugs industry. Stock solution of each drugs were prepared by dissolving an appropriate amount of chlorpropamide and valsartan in absolute ethanol. The supporting electrolyte was phosphate buffer (mixed appropriate amount of dipotassium hydrogen phosphate (K2HPO4) and potassium dihydrogen phosphate (KH2PO4).


The procedure of measurement involves the place of buffer solution in polarographic cell and the oxygen was removed by passing nitrogen gas for 5min prior the measurements, then the polarogram was recoded for known concentration of valsartan (9.8 x 10-4 M) then the sequence addition of chlorpropamide were added and then the polarogram was recorded for each addition under the optimum condition and the calibration curve was constructed.



All the electrochemical measurements were performed using a 797 polarographic analyzer computrace supplied by Metrohm, Switzerland, coupled with a three-electrodes cell, HMDE as working electrode, 1mm Pt-wire as an auxiliary electrode and Ag/AgCl.sat.KCl as reference electrode.

A digital pH-meter model pH 211 supplied by HANNA company, Portugal, was used for pH-measuring.



Valsartan gives well-defined stable reduction peak at (-1.07) V versus Ag/AgCl.sat.KCl reference electrode, the effect of pH was examined, calibration curve was constructed at the optimum conditions27.

Chlorpropamide has no reduction peak at the studied potential range so a suggested method for its indirect determination through its interaction with valsartan will be convenient for analytical purpose.


Interactions of valsartan with chlorpropamide:

A polarogram of 9.9 x 10-5 M valsartan was recorded under its optimum conditions, the polarograms were recorded for a sequence-additions of chlorpropamide stock solution (10-3 M) in phosphate buffer (pH=7) as supporting electrolyte.

The reduction peak current of valsartan decreases with increasing additions of chlorpropamide (Fig. 3).


Fig. 3: The reduction peak of valsartan (9.9x10-4 M) (a) with the sequence additions of chlorpropamide (10-3 M) (b)


The relation between reduction peak current of valsartan and chlorpropamide added concentrations in the studied concentration range was linear with R2 value = 0.9663 (Fig. 4).


The linearity of calibration curve suggest a method for the quantitation analysis of chlorpropamide.


Fig. 4: The calibration curve of chlorpropamide versus the current of valsartan (9.9x10-4 M) through interaction with chlorpropamide (stock solution 10-3 M)

Stability of interaction

To study the stability of interaction peak a voltammogram of 9.8×10-4M valsartan with 3.9×10-6M chlorpropamide was recorded under the mentioned optimum conditions of valsartan in phosphate buffer pH=7 versus time, the results obtained are shown in table 1, it is clear that the interaction reduction peak current is stable within the time studied.


Table 1: Stability of interaction reduction peak current (9.8×10-4M valsartan with 3.9×10-6M chlorpropamide) using phosphate buffer pH=7

Ip of interaction (nA)

Ep of interaction (V)

Time (min)









































Binding constant:

Binding constant was calculated according to following equation28:


ln(Ip/(Ip°-Ip)) = ln(1/([CP])) – lnK………………...….(1)


where K is the binding constant.

Ip° : the reduction peak currents of the free valsartan.

Ip : the reduction peak currents of VAL-Chlorpropamide complex.


A plot of ln(Ip/(Ip°-Ip)) versus ln(1/[CP]) gives a linear relationship with R2 value = 0.9635, the intercept represent the binding constant which equal 8.8851 M-1 (Fig. 5).


Fig.5: Plot of ln (Ip/( Ipº –Ip)) vs ln (1/[CP]) in high concentration


Calibration curve at low concentration:

To obtain lower detection limit of chlorpropamide through its interaction with valsartan, a sequence-additions of chlorpropamide (stock solution 10-5 M) were added to the polarographic cell containing 9.9 x 10-6 M valsartan and the polarograms were recorded under the optimum conditions (Fig. 6).


Fig. 6: The reduction peak of valsartan (9.9 x 10-6 M) (a) with the sequence additions of chlorpropamide (10-5 M) (b)


The results obtained are shown in figure 7 and figure 8.


Fig.7: Plot of ln (Ip/( Ipº –Ip)) vs ln (1/[CP]) in low concentration



Fig. 8: The calibration curve of chlorpropamide versus the current of valsartan (9.9 x 10-6 M) through interaction with chlorpropamide (stock solution 10-5 M)


The detection limit of chlorpropamide was 4.89x10-9 M.



The chlorpropamide can be indirectly determine by its interaction with valsartan. The suggest method was simple, sensitive and accurate, so through our suggested method we reached low concentrations of chlorpropamide (4.89x10-9 M).



The authors are grateful to the chemistry department, college of sciences, Mosul university.



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Received on 12.02.2020            Modified on 27.01.2021

Accepted on 30.05.2021           © RJPT All right reserved

Research J. Pharm. and Tech 2021; 14(12):6541-6544.

DOI: 10.52711/0974-360X.2021.01131