Differential Pulse Polarographic Behavior and Determination of Simvastatin in Pure and Pharmaceutical Dosage Forms Using Dropping Mercury Electrode

 

Abdul Aziz Ramadan*, Hasna Mandil**, Nidal Ashram

Department of Chemistry, Faculty of Science, University of Aleppo, Syria.

 

ABSTRACT:

The differential pulse polarographic behavior and determination of simvastatin (SMV) in pure and pharmaceutical dosage forms were investigated on dropping mercury electrode (DME). The method involves the reduction behavior of SMV has been studied in different supporting electrolytes within the pH range 3–9 at DME by differential pulse polarographic analysis (DPPA). The best definition of the analytical signals was found in sodium acetate buffer at pH 7.5 at -1378 to -1384 mV (vs. Ag/AgCl). Under optimized conditions ^{the peak current (Ip)} is linear over the range 0.1256- 8.731 μg.mL^-1. The DPPA was used successfully for the determination of SMV in pure form. The relative standard deviation did not exceed 4.6% for the concentration of SMV 0.12556 μg.mL^-1. Regression analysis showed a good correlation coefficient (R²=0.9997) between Ip and concentration over the mentioned range. The limit of detection (LOD) and the limit of quantification (LOQ) were to be 0.015 μg.mL^-1 and 0.045 μg.mL^-1, respectively. The proposed method was validated for linearity, precision and accuracy, repeatability, sensitivity (LOD and LOQ), robustness and specificity with average recovery of 99.7-100.7%. The developed method is applicable for the determination of SMV in pure and different dosage forms with assay 99.0-103.0% and the results are in good agreement with those obtained by the HPLC reference method.

 

 

 

INTRODUCTION:

Simvastatin reduces levels of circulating atherogenic lipoproteins by competitive inhibition of the microsomal enzyme 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, a critical intermediary in the biosynthesis pathway of cholesterol [1]. Also, simvastatin inhibits oxidation of native and modified low-density and high-density lipoproteins [2]. So, it is used in the treatment of hypercholesterolemia [3]. SMV is soluble (mg/mL) in chloroform, DMSO, methanol, ethanol and insoluble in water. The molecular formula of SMV is C₂₅H₃₈O₅ and the molecular weight

Scheme 1: Chemical structure of cefpodoxime proxetil (CEFP).

 is 418.574 g/mol [4], see Scheme 1.

 

Scheme 1: Chemical structure of Simvastatin (SMV).

 

The electrochemical oxidation behavior and analytical assay of simvastatin (SMV) in pharmaceuticals using voltammetric techniques was proposed [5]. Stationary GCE was used for the differential pulse polarographic (DPV) and square-wave voltammetry (SWV) determination of SMV in tablets and biological samples [6]. In study, the serum proteins and endogenous substances in serum and urine samples were precipitated by the addition of acetonitrile, the mixture was centrifuged, and the supernatant was taken and diluted with the 0.1 M H₂SO₄ and 20% methanol and directly analyzed. The detection limit of SMV is 2.71×10^-7 and 5.50×10^-7 M for DPV and SWV methods respectively.

 

GCE modified with electropolymerized film of p-toluene sulfonic acid (p-TSA) [7], sodium dodecyl benzene sulfonate (SDBS) [8] and for simultaneous determination of SMV and Gemfibrozil in pharmaceuticals. Electrocatalytic effect of the oxidation of SMV by CV was observed in the mix of 0.1 M H₂SO₄ 10% ethanol [7,8] and in 0.1 M acetate buffer solution at pH 5.5 [9].

 

Simvastatin was studied and determined using mercury electrodes [10-12]. The electrochemical characteristics of solid and dissolved SMV were investigated by CV and SWV on paraffin-impregnated graphite electrode (PIGE) and SMDE. Solid microparticles of SMV were mechanically immobilized on the surface of graphite electrode and immersed into aqueous electrolyte. The microparticles were oxidized at 1.1 V in a totally irreversible electrode reaction. Simvastatin dissolved in acetonitrile and mixed with 0.1 M Na₂B₄O₇-KH₂PO₄ aqueous buffer solution at pH 7 is strongly adsorbed on the surface of mercury electrode. Adsorbed SMV was reduced at-1.45 V in the fast and reversible electrode reaction followed by a chemical reaction[10]. The electrochemical reduction of SMV at a hanging mercury drop electrode (HMDE) was investigated SWV and abrasive stripping voltammetry (ASV) with PIGE. A reduction peak was observed at -800 mV with 60 s accumulation time. The method can be employed for the quantification of SMV in pharmaceuticals and biological fluids [11].

 

The electrochemical reduction of SMV-Cd (II) complex at a HMDE in BR buffer containing Cd (II). A reduction peak was observed at -1000 mV with 30 s accumulation time. The detection limit of simvastatin is 2.2×10^-10 M, the mean recovery of four measurements 97±2.16%. The electrode was used for the determination of SMV in human urine and plasma [12].

 

Several analytical methods have been reported for the determination of simvastatin, which include HPLC [13-16], HPLC-MS/MS [17], derivative spectrophotometry [18].

 

In the present work, development and validation of differential pulse polarographic determination of Simvastatin in pure and pharmaceutical dosage forms using dropping mercury electrode was applied. The method is easy, fast, accurate and sensitive for the determination of this compound in pharmaceutical formulations.

 

EXPERIMENTAL:

Reagents:

Working reference standard of simvastatin (99.5%) was supplied by D.K. Pharmachem Pvt. Ltd (INDIA), (Mfg. 12-2014, Exp. 11-2019). Lithium perchlorate trihydrate, di-Sodium tetraborat decahydrat (borax), di-sodium hydrogen phosphate dodecahydrate, sodium acetate trihydrate, sodium hydroxid, perchloric acid 70%, ortho-phosphoric acid (85%), acetic acid (100%), methanol, ethanol (absolute) were of GR for analysis purchased from MERCK.

 

Instruments and apparatus:

A Metrohm 746 VA processor, A Metrohm 747 VA stand with a dropping mercury electrode (DME) as a working electrode, an auxiliary platinum electrode and a reference electrode, double junction type, (vs. Ag/AgCl) saturated with a 3.0 M KCl solution and the three-electrode cell were used. All measurements were done at room temperature 25±5^oC. Highly pure nitrogen gas (99.999 %) was used for de-oxygenation. pH meter from Radiometer company model ion check was used for the studying and monitoring the pH effects. The diluter pipette model DIP-1 (Shimadzu), having 100 μL sample syringe and five continuously adjustable pipettes covering a volume range from 20 to 5000 μL (model PIPTMAN P, GILSON), were used to prepare the experimental solutions. A ultrasonic processor model powersonic 405 was used to sonicate the sample solutions. Electronic balance (Sartorius-2474; d=0.01 mg) was used for weighing the samples.

 

Supporting electrolyte:

sodium acetate-acetic acid (HAc-NaAc), Britton Robinson, H₃PO₄-Na₂HPO₄, disodium tetraborat, lithium perchlorate buffer, buffer 0.2000 mol.L^-1 at pH 7.5.

 

A stock standard solution of simvastatin (1 x 10^-3 Mol. L^-1)

This solution was prepared by dissolving 21.04 mg of simvastatin in 50 ml methanol (1x10^-3 mol.L^-1), then diluting 1.000 ml from this solution to 10 ml (1x10^-4 mol.L^-1).

 

Working solutions:

The stock solutions were further diluted to obtain working solutions daily just before use in the ranges of SMV: 0.300, 0.500, 1.000, 2.000, 4.000, 6.000, 8.000, 10.000 14.00 16.00 and 20.000 μmol.L^-1 (0.1256, 0.2093, 0.4187, 0.83721, 1.6742, 2.5114, 3.3486, 4.1857, 5.860, 6.6971 and 8.3714 μg.mL^-1) by dilution of the volumes: 0.075, 0.125, 0.250, 0.500, 1.000, 1.500, 2.000, 2.500, 3.500, 4.000 and 5.000 mL from stock standard solutions which were transferred into a 25 ml volumetric 7.5 mL of supporting electrolyte were added, and diluted with double distilled deionized ^water to the mark. Ultrapure mercury from Metrohm Company was used throughout the experiments.

 

^{Sample preparation:}

^{A commercial formulations (as tablet) were used for the analysis of SMV by using} DPPA ^with DME ^{The pharmaceutical formulations were subjected to the analytical procedures:}

 

^{(1)        Zocorine coated tablets, ASIA Pharmaceutical Industries., Aleppo–Syria, each Tablet contains: 10 and 20 mg of SMV (Mfg. 05. 2016, Exp. 05. 2018).}

^{(2)        Simvacor coated tablets, ALFARES Pharmaceutical Industries., Damascus–Syria, each Tablet contains: 20 mg of SMV (Mfg. 07. 2017, Exp. 07. 2019).}

 

^{Stock solutions of pharmaceutical formulations:}

Contents of 20 tablets of each studied pharmaceutical formulation were weighted accurately, crushed to a fine powder and mixed well. An amount equivalent to a weight of one tablet, was solved in 20 mL ethanol by using ultrasonic, filtered over a 50 mL flask and diluted to 50 mL with ethanol, the resulting solution contains the follows: 200 and 400 μg.mL^-1 for all studied pharmaceutical formulations content 10 and 20 mg/tab., respectively.

 

^{Working solutions of pharmaceuticals:}

^{These solutions were prepared daily by diluting 500 and 250µL from stock solutions of each pharmaceutical formulations} for contents: 10 and 20 mg/tab, respectively^{, adding 7.50 mL from supporting electrolyte and diluting to 25 mL with} double distilled deionized ^{water, these solutions} contain ^4.00 μg.mL^{-1 of SMV.}

 

^{Analytical procedure:}

25 mL of working solutions of simvastatin or working solutions of pharmaceuticals was transferred to the cell. The solution was deoxygenated with N₂ gas for 300 s. The studied potential range was from –800 to –1600 mV versus Ag/AgCl with differential pulse polarographic analysis using dropping mercury electrode in the optimum conditions were applied.

 

Results and discussion:

^{Differential pulse polarographic behavior:}

^{The polarograms for concentration 0.30-20.0 µmol.L-1 (0.1256- 8.3714} μg.mL^{-1) of SMV in the optimal conditions (supporting electrolytes, pH, scan rate, initial potential, final potential, etc.) using DPPA at} DME ^{were studied. The best definition of the analytical signals was found in sodium acetate (0.06 M) buffer at pH 7.5 at      -1379 to -1384mV (versus Ag/AgCl).}

 

 

The effect of supporting electrolyte concentration:

It was not obvious from the literature as to the particular choice of supporting electrolyte or its concentration. The electrochemical reduction of simvastatin was studied in various supporting electrolytes such as sodium ^{acetate trihydrate (}HAc-NaAc), Britton Robinson, H₃PO₄-Na₂HPO₄, disodium tetraborat, lithium perchlorate buffer on the peak current (Ip) and Ep was studied at pH 7.5. Simvastatin yielded a single reduction peak in all the above supporting electrolytes, the values of Ep were -1381, -1384, -1388, -1392 and -1466 mV for the ^{mention buffers, respectively, see Figure 1. However, the best results were} obtained with HAc-NaAc. The effect of the concentration of HAc-NaAc was tested over the 10, 15, 25. 30, 35, 40, 50, 60, 70, 80, 90 and 100 mM. The DPPA at DME of 8.0 µM of SMV with the varying concentrations of supporting electrolyte, shown in Fig. 2.

 

^{The effect of pH:}

The influence of pH from 3.0 to 9.0 using different buffer solutions on I_p and E_p was studied. The best definition of the analytical signals was found in sodium acetate trihydrate (0.06M) buffer (pH 7.5). The values of I_p increase with increasing pH value of 4.5 to 6.5, then become semi-fixed until pH 8.5, and finally decrease until pH 9.5. A pH value of 7.5 was optimal for SMV as the peak current (I_p) was the highest at this pH value, see fig.3,a. While E_p values were almost constant, see fig.3,b.

 

 

Fig.1.The effect of buffer solutions on polarograms of SMV (8.00 µM) using DPPA at DME ^{(0.06 M) buffers:1-NaCH3COO. 3H2O, 2-}Britton-Robinson^, 3-Na₂HPO₄. 12H₂O, 4-Na₂B₄O₇. 10H₂O, 5-^{LiClO4. 3H2O} (Purge gas N₂, purge time 300 s, sweep rate 5 mV/s, U. amplitude-60 mV, t. meas. 32 ms, t. pulse 45 ms, t. step 1.6 s, U. step 8 mV, temperature 25°±5°C).

 

 

 

 

 

Fig.2. The effect of the concentration of NaCH₃COO. ₃H₂O on polarograms of SMV (8.00 µM) using DPPA at DME (Purge gas N₂, purge time 300 s, sweep rate 5 mV/s, U. amplitude-60 mV, t. meas. 32 ms, t. pulse 45 ms, t. step 1.6 s, U. step 8 mV, temperature 25°±5°C).

 

 

Fig.3,a. The effect of pH solution on Ip of SMV (8,00 µM) using DPPA at DME ^{containing buffer (0.06 M)} 1-lithium perchlorate trihydrate, 2-Na₂HPO₄. 12H₂O, 3-Na₂B₄O₇. 10H₂O, 4-^{NaCH3 COO. 3H2O, 5-}Britton-Robinson (Purge gas N₂, purge time 300 s, sweep rate 5 mV/s, U. amplitude-60 mV, t. meas. 32 ms, t. pulse 45 ms, t. step 1.6 s, U. step 8 mV, temperature 25°±5°C).

 

 

Fig.3,b. The effect of pH solution on Ep of SMV (8,00 µM) using DPPA at DME ^{containing buffer (0.06 M)} 1-lithium perchlorate trihydrate, 2-Na₂HPO₄. 12H₂O, 3-Na₂B₄O₇. 10H₂O, 4-^{NaCH3COO.3H2O, 5-}Britton-Robinson (Purge gas N₂, purge time 300 s, sweep rate 5 mV/s, U. amplitude-60 mV, t. meas. 32 ms, t. pulse 45 ms, t. step 1.6 s, U. step 8 mV, temperature 25°±5°C).

 

The effect of negative pulse amplitude (U ampl.):

The effect of negative pulse amplitude (U ampl.) between-10 to-100 mV on I_p and Ep was studied. I_p linearly increases with increasing amplitude value until -70 mV and then increases slowly, see fig.4.

 

^{The effect of initial and final potential:}

^{The effect of initial and final potential on the Ip and Ep was studied. It was found that the best initial potential was -800 mV and better final potential was -1600 mV.}

 

^{The effect of temperature and time:}

^{The effect of temperature and time on the electrochemical reaction of} SMV ^{was studied at different values (15-35oC, 5-60 min) by continuous monitoring of the Ip. It was found that, the value of Ip was not affected by temperature between 20 to 30oC (the temperature 25±5°C was used). The effect of waiting time was determined at laboratory ambient temperature (25±5°C). It was found that, the value of Ip was not affected by time between 5 to 60 min.}

 

The effect of time pulse (t. pulse):

The effect of time pulse (35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95 and 100 ms) on polarograms was as the follows: I_p decreases with increasing time pulse and E_p has become increasingly latency positive value (-1380 to-1388 mV) with increasing t. pulse. The peak was more symmetrical when the t. pulse value of 45 ms.

 

 

Fig.4. The effect of ^{negative pulse amplitude (U ampl.)} on Ip and Ep of SMV (8.00 µM) using DPPA at DME (Purge gas N₂, purge time 300 s, sweep rate 5 mV/s, U. amplitude-60 mV, t. meas. 32 ms, t. pulse 45 ms, t. step 1.6 s, U. step 8 mV, temperature 25°±5°C).

 

The effect of time interval for voltage step (t. step)

I_p linearly increases with increasing t. step (0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.4, 1.5, 1.6, 1.8, 2.0, 2.2 and 2.5 s), while E_p has become increasingly latency positive value (-1387 to -1375 mV) with increasing t. step. The value of the preferred t. step was 1.6 s.

 

The effect of measurement time (t. meas.)

I_p increases with increasing  t. meas. (4, 8, 12, 16, 20, 24, 28 and 32 ms), while E_p remains quasi-static. The value of the preferred  t. meas. was 32 ms. ^{The optimum parameters established for determination of SMV using DPPA at} DME ^{are shown in Table 1.}

 

Table 1. The optimum parameters established for determination of SMV using DPPA at MDE.

parameters	Operating modes
Working electrode	Dropping mercury electrode (DME)
Supporting electrolytes (buffer)	0.06 M sodium acetate trihydrate
pH	7.5
Medium	double distilled deionized water
Value of pulse amplitude	-60 mV
Purge gas	Pure N2
Purge time	300 s
Initial potential	-800 mV
Final potential	-1600 mV
Scan rate	5 mV/s
t. meas.	32 ms
t. pulse	45 ms
t. step	1.6 s
Temperature of solution	25°± 5°C

 

Calibration curves:

Calibration curves for the determination of simvastatin using differential pulse polarographic analysis at dropping mercury electrode with negative amplitude in sodium acetate ^{trihydrate (0.06 M) buffer at pH 7.5} were applied. One reduction peak was observed in the range        -1379 to -1384 mV (E_p). The peak current (I_p) was proportional to the concentration of SMV over the ranges  0.1256-8.3714 μg.mL^-1 (0.300-20.000 μmol.L^-1). The polarograms in the optimum conditions using DPPA at DME of SMV at different concentrations are shown in Fig.5. The regression equation and correlation coefficient (R²) were as the follows: y=-3.3174x-0.2205, R²=0.9997; where y: I_p, nA (I_p=I_p,total- I_elect.; where I_elect. is electrolyte current at E^p) and x: C_SMV, μg.mL^-1, see Fig.6.

 

^{Analytical results:}

Determination of SMV using DPPA at DME in the optimum conditions using analytical curves, I_p=f (C_SMV), showed that the accuracy was ready over the ranges of SMV concentration between 0.1256-8.3714 μg.mL^-1 (0.300–20.000 μmol.L^-1). The relative standard deviation (RSD) was not more than 3.6%, see Table 2. Limit of detection (LOD) and limit of quantitation (LOQ) for the determination of SMV by this method were as the follows: 0.01465 μg.mL^-1 (3.500x10^-8 M) and 0.0444 μg.mL^-1 (1.061x10^-7M), respectively, while the LOD were 2.71x10^-7 M and 4.50 x10^-9 M by using optimized conditions of SWV on GCE and HMDE respectively [9-11].

 

 

Fig. 5. The polarograms in the optimum conditions using DPPA on DME of SMV in sodium acetate trihydrate (0.06 M) buffer at pH 7.5 at concentrations: 1-0; 2-0.3; 3-0.5; 4-1.0; 5-2.9; 6-4.0; 7-6.0; 8-8.0; 9-10; 10-14; 11-16 and 12-20 μM.

 

 

Fig.6. ^{Calibration curve for the determination of} SMV ^{using DPPA on} DME in the optimum conditions (I^p =I^p,total-I^elect.)^.

 

APPLICATIONS:

Many applications for the determination of simvastatin in some Syrian pharmaceutical preparations using differential pulse polarographic analysis on mercury drop electrode with negative amplitude in sodium ^{acetate trihydrate (0.06 M) buffer at pH 7.5 according to the optimal conditions were proposed. The} amount (m) of SMV in one capsule was calculated from the following relationship: m=h. m', where: m' is the amount of SMV in tablet calculated according to the regression equation of calibration curve, h conversion factors are equal to 2. 5, 5, 10 for all pharmaceuticals content 10, 20 and 40 mg/tab, respectively. The results of quantitative analysis for SMV in pharmaceutical preparations were summarized in Tables 4. The proposed method was simple, direct and successfully applied to the determination of SMV in pharmaceuticals without any interference from excipients. Average recovery ranged between 99.0 to 105.0%. The results obtained by this method agree well with the contents stated on the labels and were validated by HPLC method[16]. Therefore, the presented method can be recommended for routine analysis of simvastatin in pharmaceutical formulations.

 

 

Table 2. Determination of simvastatin using differential pulse polarographic analysis on DME with negative amplitude in sodium acetate trihydrate (0.06 M) buffer at pH 7.5.

*n=5, t=2.776

Table 3. Determination of SMV in some Syrian pharmaceutical preparations using DPPA on DME with negative amplitude in sodium acetate trihydrate (0.06 M) buffer at pH 7.5 according to the optimal condition.

Tablet dosage form	Label Claim of SMV, mg/tab.	*Mean±SD (as SMV), mg/ tab.	RSD%	Assay%	* (Assay%), by HPLC [16]
Zocorine	10	9.9 ±0.26	2.6	99.0	99.5
	20	20.2±0.48	2.4	101.0	102.0
Simvacor	20	20.6±0.47	2.3	103.0	102.5

*n=5, Assay=(found mean/label claim)x100.

 

Method validation:

The developed method for simultaneous estimation of SMV has been validated in accordance with the International Conference on Harmonization guidelines (ICH) [19].

 

Selectivity:

Selectivity test determines the effect of excipients on the assay result. To determine the selectivity of the method, standard solution of SMV were analyzed. The results of the tests proved that the other components of the drug did not produce any interfere.

 

Linearity:

Several aliquots of standard stock solution of SMV were taken in different 25 ml volumetric flasks such that their final concentrations were 0.1256-8.3714 μg.mL^-1 for SMV using DPPA at DME in sodium acetate trihydrate ^{(0.06 M) buffer at pH 7.5}. Linearity equation obtained was y=-3.3174x-0.2205 for the mentioned range (R²=0.9997).

 

Precision and Accuracy:

The precision and accuracy of proposed method was checked by recovery study by addition of standard drug solution to pre-analyzed sample solution at three different concentration levels (80%, 100% and 120%) within the range of linearity for SMV. The basic concentration level of sample solution selected for spiking of the SMV standard solution was 2.5114 μg.mL^-1. The proposed method was validated statistically and through recovery studies, and was successfully applied for the determination of SMV in pure and dosage forms with percent recoveries ranged from 99.7% to 100.8%, see Table 4.

 

Table 4. Results of recovery studies (n=5).

Level	% Recovery
80%	100.5
100%	99.7
120%	100.8

 

Repeatability:

The repeatability was evaluated by performing 10 repeat measurements for 2.5114 μg.mL^-1 of SMV using the studied DPPA at DME sodium acetate trihydrate ^{(0.06 M) buffer at pH 7.5} under the optimum conditions. The found amount of SMV (±SD) was 2.5030±0.05006 μg.mL^-1 and the percentage recovery was found to be 100.5±2.0 with RSD of 0.020. These values indicate that the proposed method has high repeatability for SMV analysis.

 

Sensitivity (limit of detection [LOD] and limit of quantitation [LOQ]):

The sensitivity of the presented method was evaluated by determining the LOD and the LOQ. of SMV by this method were as the follows: 0.015 μg.mL^-1 and 0.045 μg.mL^-1, respectively.

 

 

 

Robustness:

The robustness of the method adopted is demonstrated by the constancy of the absorbance with the deliberated minor change in the experimental parameters such as the change in the concentration of excipients, buffer (±10%), temperature (±5^oC) and waiting time (30 min).

 

Specificity:

The specificity of the method was ascertained by analyzing standard SMV in presence of excipients. These findings prove that the suggested methods is specific for determination of the investigated drugs without interference from the coformulated adjuvants.

 

Interferences:

Resovastatin does not interfere, while ezetimibe and atorvastatin interfere.

The homogenization of tablets:

The homogenization of tablets in terms of the weight and the amount of drug was studied. It found that the mean weight and amount drug in the tablets was 0.1852±0.0018 g (i.e.±0.98%) and 0.1844±0.0005 g (i.e.±0.27%) for Zocorine tablets (10 and 20 mg/tab), respectively, and 0.2325±0.0052 mg (i.e.±2.24%) for Simvacor tablets (20 mg/tab). While the mean amount drug in the tablets was 9.9^±0.26 mg (i.e.±2.6%) and 20.2±0.48 mg (i.e.±2.4%) for Zocorine tablets (10 and 20 mg/tab), respectively, and 20.6±0.67 mg (i.e.±3.4%) for Simvacor tablets (20 mg/tab); which shows that homogeneity of tablets is acceptable.

 

Conclusion:

Electrochemical behavior and DPPA of SMV in pure form and in pharmaceutical preparations using DME with  sodium acetate ^{trihydrate (0.06M) buffer at pH 7.5 according to the optimal} conditions was applied. One reduction peak was observed. Ip is linear over the range 0.1256-8.3714 μg.mL^-1; which makes this method more sensitive compared to what is available in the literatures[9, 10]. The relative standard deviation did not exceed 3.6% for the concentration 0.1256 μg.mL^-1 of SMV. Regression analysis showed a good correlation coefficient (R²=0.9997) between Ip and concentration over the mentioned range. The proposed method was successfully applied to the direct analysis of SMV in pharmaceutical formulations without any interference from excipients and with adequate accuracy and sensitivity without any pre-separation such as extraction.

 

CONFLICT OF INTERESTS

The authors have declared that no conflict of interests exists.

 

References:

1        The United States Pharmacopoeia 25, The National Formulary 20, United States Pharmocopocial Convention. Inc 2002; 9: 571-572.

2        Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344:1383–1389.

3        MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20, 536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22.

4        British Pharmacopeia, Stationary Office, London, 2004;928-1415.

5        Zhang, H, Hu, C, Wu S, Hu S. Enhanced oxidation of simvastatin at a multi-walled carbon nanotubes-dihexadecyl hydrogen phosphate composite modified glassy carbon electrode and the application in determining simvastatin in pharmaceutical dosage forms. Electroanalysis.2005;17:749-754.

6        Coruh Ö, Özkan SA. Determination of the antihyperlipidemic simvastatin by various voltammetric techniques in tablets and serum samples. Pharmazie. 2006;61:285-290.

7        Deepa MB, Mamatha GP, Naik AY, Sherigara BS. Cyclic voltammetric studies of simvastatin at glassy carbon electrode modified with poly(p-toluene) sulfonic acid. Int. J. Pharm. Chem. 2013;3: 9-16.

8        Deepa MB, Mamatha GP, Arthoba Naik Y, Sherigara BS, Manjappa S, Vijaya B. Electrochemical studies of simvastatin at glassy carbon electrode and immobilized by sodium dodecyl sulfate surfactant. J. Chem. Pharm. Res. 2012;4:2803-2816.

9        Deepa MB, Mamatha GP, Naik YA, Sherigara BS. Simultaneous electrocatalytic determination of simvastatin and gemfibrozil at poly (glycine) modified glassy carbon electrode. IJCPS. 2012;3: 60-69.

10      Komorsky-Lovrić Š, Nigović B. Electrochemical characterization of simvastatin by abrasive stripping and square-wave voltammetry. J. Electroanal. Chem. 2006;593:125-130.

11      Nigović B, Komorsky-Lovrić Š, Devčić Dubravka. Rapid voltammetric identification and determination of simvastatin at trace levels in pharmaceuticals and biological fluid. Croat. Chem. Acta. 2008;81:453-459.

12      Al-Ghamdi AF, Hefnawy MM, El-Shabrawy Yasser. Non-extractive ultra-trace determination of simvastatin in biological fluids by voltammetric method via complexation with cadmium. Dig. J. Nanomater. Bios. 2014;9:355-368.

13      Yang HT, Feng Y, Luan YW. Determination of simvastatin in human plasma by liquid chromatography-mass spectrometry. J Chromatogr B 2003; 785: 369–375.

14      Miao XS, Metcalfe CD. Determination of cholesterol-lowering statin drugs in aqueous samples using liquid- chromatography-electrospray ionization tandem mass spectrometry. J Chromatogr A. 2003; 998:133–141.

15      Kim BC, Ban E, Park JS, Song YK, Kim CK Determination of simvastatin in human plasma by switching HPLC with UV detection. J Liq Chromatogr Rel Tech. 2004; 27: 3089–3102.

16      Carlucci G, Mazzeo P, Biordi L. Simultaneous determination of simvastatin and its hydroxy acid form in human plasma by high-performance liquid chromatography with UV detection. J Pharm Biomed Anal. 1992b;10: 693–697.

17      Wang L, Asgharnejad M. Second-derivative spectrophotometric determination of simvastatin in its tablet dosage form. J Pharm Biomed Anal. 2000;21: 1243–1248.

18      Carlucci G, Mazzeo P. Determination of simvastatin in pharmaceutical dosage forms by HPLC and derivative UV-spectrophotometry. Farmaco.1992a; 47: 817–823.

19      ICH: Proceedings of the International Conference on Harmonization of Technical Requirement of Registration of Pharmaceuticals for Human Use (ICH Harmonized Tripartite Guidelines).

 

Accepted on 29.05.2018      © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(7): 2888-2894.