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: amerthanon@yahoo.com, aws.alhafidh@gmail.com

 

ABSTRACT:

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.

 

 


INTRODUCTION:

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.

 

MATERIAL AND METHODS:

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.

 

Instrumentation:

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.

 

RESULTS AND DISCUTION:

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)

309

-1.1

0

307

-1.1

5

307

-1.1

10

308

-1.1

15

309

-1.1

20

309

-1.1

25

308

-1.1

30

306

-1.1

35

305

-1.1

40

305

-1.1

45

306

-1.1

50

306

-1.1

55

305

-1.1

60

 

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.

 

CONCLUSION:

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).

 

ACKNOWLEDGEMENT:

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

 

REFERENCES:

1.      Foster RW. Basic Pharmacology. Published by Butterworth Heinemann Ltd., London. 1991; 3rd ed: p. 186.

2.      Dinnendahl V, Fricke U. Arzneistoff-Profile. Govi Pharmazeutischer Verlag, Eschborn, Germany. 2010; 4(23ed): ISBN 978-3-7741-9846-3.

3.      Odunola MTB, Enemali IS, Garba M, Obodozie OO. Rapid High Performance Liquid Chromatographic Determination of Chlorpropamide in Human Plasma. African Journal of Biotechnology. 2007; 6(12): 1378–1381.

4.      Kishikawa N, Hammad FS, Ohyama K, Kubo K, Mabrouk MM, Nakashima K, Kuroda N. HPLC Determination of Chlorpropamide in Human Serum by Fluorogenicderivatization Based on The Suzuki Coupling Reaction with Phenylboronic Acid. Chromatographia. 2013; 76(11-12): 703-706.

5.      Basavaiah K, Rajendraprasad N. High Performance Liquid Chromatographic Assay of Chlorpropamide, Stability Study and its Application to Pharmaceuticals and Urine Analysis. Austin Journal of Analytical and Pharmaceutical Chemistry. 2017; 4(1): 1082

6.      The British Pharmacopeia. Vol. III. Her Majesty Stationary Office, London. 2008: p. 2530.

7.      Mbah CJ, Okorie NH. Spectrophotometric Determination of Chlorpropamide in Bulk and Dosage Form by Complexation with Chloranilic Acid. Journal of Scientific Research. 2011; 3(1): 207-212.

8.      El-Bardicy MG, El-Khateeb SZ, Assad HN, Ahmed AS. Mercurimetric Determination of Chlorpropamide by Back Titration. Indian Journal of Pharmaceutical Sciences. 1988; 50(3): 171-172.

9.      Nourrudin AW, Abdelwahab NS, El-Zeiny BA, Tohamy SI. Stability Indicating TLC-Densitometric Method for Determination of Chlorpropamide. Journal of Liquid Chromatography and Related Technology. 2013; 36(11): 1575-1585.

10.   Anna G, Hanna H, Anna B, Dorota K. Normal- and Reversed-Phase Thinlayer Chromatography of Seven Oral Antidiabetic Agents. Journal of Planar Chromatography- Modern TLC. 2003; 16(4): 271-275.

11.   Khalid S, Khawla S. Gas Chromatographic Method for Determination of Tolbutamide and Chlorpropamide. Journal of Pharmaceutical Sciences. 1970; 59(6): 782-784.

12.   Nasierowska Z, Suffczynski J, Szyszko E, Taton J, Kolinski P, Czech A, Wojterska J. Modification of The Gas Chromatographic Method for Blood Chlorpropamide Determination and Evaluation of Its Use for Clinical and Pharmacological Purposes. Polish Journal of Pharmacology and Pharmacy. 1983; 35(5): 405-415.

13.   El-Sayed MA, Agarwal SP. Spectrophotometric Determination of Atropine, Pilocarpine and Strychnine with Chloranilic Acid. Talanta. 1982; 29(6): 535-537.

14.   Chitlange SS, Bagri K, Sakarkar DM. Stability Indicating RP- HPLC Method for Simultaneous Estimation of Valsartan and Amlodipine in Capsule Formulation. Asian Journal of Research in Chemistry. 2008; 1(1): 15-18.

15.   Gawai MN, Aher SS, Saudager RB. New UV – Spectrophotometric Method Development and Validation of Valsartan in Bulk and Pharmaceutical Dosage Forms. Asian Journal of Research in Chemistry. 2016; 9(9): 441-444.

16.   Yogeshwar RM, Ramesh V, Kista RCh, Venugopal N, Saravanan G, Suresh Y, Suryanarayana M, Debashish D, Raju B. Low-Level Determination of Residual 4-Bromo Methyl-2'-Cyanobiphenyl in Valsartan by Liquid Chromatography-Mass Spectrometry. Asian Journal of Research in Chemistry. 2010; 3(2): 407-410.

17.   Shinde SR, Bhoir SI, Pawar NS, Bhagwat AM. Quantitation of Valsartan in Human Plasma by High Performance Liquid Chromatography with Fluorescence Detection and its Application to Bioequivalence Study. Research Journal of Pharmacy and Technology. 2009; 2(3): 487-490.

18.   Singh SM, Topagi KS, Damle MC. A Validated High Performance Thin Layer Chromatographic Method for Simultaneous Estimation of Nebivolol Hydrochloride and Valsartan in Pharmaceutical Dosage Form. Research Journal of Pharmacy and Technology. 2009; 2 (4): 746-749.

19.   Vaidya N, Choure R. Electrochemical Analysis of Fatty Acids Obtained from the Natural Resource Seed of Perilla frutescens. Asian Journal of Research in Chemistry. 2011; 4(5): 705-707.

20.   Kumar PCR, Naidu GRK, Sridevi C, Reddy CS. Electrochemical Reduction Behaviour of Guanethidine. Asian Journal of Research in Chemistry. 2011; 4(12): 1928-1929.

21.   Ramadan AA, Mandil H, Abu-Saleh R. Electrochemical Behavior and Differential Pulse Polarographic Determination of Flucloxacillin in Pure and Pharmaceutical Dosage Forms Using Dropping Mercury Electrode. Research Journal of Pharmacy and Technology. 2019; 11(8): 3313-3319.

22.   Ramadan AA, Mandil H, Ashram N. Differential Pulse Polarographic Behavior and Determination of Simvastatin in Pure and Pharmaceutical Dosage Forms Using Dropping Mercury Electrode. Research Journal of Pharmacy and Technology. 2018; 11(7): 2888-2894.

23.   Singh J, Sharma SK. Electrochemical behaviour of In(III) with Isoleucine in aqueous and non-aqueous media at Dropping Mercury Electrode. Asian Journal of Research in Chemistry. 2018; 11(2): 391-394.

24.   Mohapatra SS, Kafle A, Reddy I, Sarma J. Drug Interactions with Antibiotics. International Journal of Chemical Studies. 2018; 6(2): 2120-2122.

25.   Monago CC, Gozie GC, Joshua PE. Antidiabetic and Antilipidemic Effects of Alkaloidal Extract of Emilia sonchifolia in Rat. Research Journal of Science and Technology. 2010; 2(3): 51-56.

26.   Bhavimani G, Nitin M. Pharmacological Studies on Drug-Drug Interactions between Antidiabetic Drug (Glibenclamide) and Selective Anti-HIV Drug (Lamivudine) in Rats and Rabbits. Research Journal of Pharmacology and Pharmacodynamics. 2017; 9(3): 117-121

27.   Alhafidh AZ, Altaee AT. Electrochemical Behavior of Valsartan, Glibenclamide and Their Interaction with Each Other Using Square Wave Voltammetry. Rafidain journal of science. 2019; 28(2): 64-75.

28.   Jalali F, Dorraji PS. Electrochemical and Spectroscopic Studies of The Interaction Between the Neuroleptic Drug, Gabapentin, and DNA. Journal of Pharmaceutical and Biomedical Analysis. 2012; 70: 598-601.

 

 

 

 

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