Research article · 2025 · Full text
International Journal of Advanced Chemistry ResearchElectrochemical profiling and analytical method validation of bismuth subsalicylate in marketed pharmaceutical formulation via cyclic voltammetry
Volume 7(6) · Pages 01–07 · DOI: 10.33545/26646781.2025.v7.i6a.283 ↗
Research areasElectrochemical Analysis and ApplicationsAnalytical Methods in PharmaceuticalsInorganic and Organometallic Chemistry
Abstract
Author-writtenBismuth subsalicylate (BSS) is a metallopharmaceutical drug commonly used as an antidiarrheal agent. Traditional analytical methods for metallopharmaceutical often require long analysis times, high reagent use, and costly equipment. To address these issues, a cyclic voltammetry (CV) method was developed for BSS determination. The measurements used a potentiostat with a glassy carbon electrode (GCE) and Britton-Robinson Buffer (0.04 M, pH 9.0) as the supporting electrolyte. A platinum auxiliary electrode and Ag/AgCl (3 M KCl) as the reference electrode, completed the setup. BSS showed an irreversible redox reaction at the GCE. Optimal CV parameters included a scan rate of 0.05 V/s and potential range from -0.1 to 1.5 V. The method showed linearity from 2 to 18 ppm with an R² of 0.997. Limits of detection and quantification were 0.159 ppm and 0.483 ppm, respectively. Tablet analysis gave recoveries with mean content (%) ± SD ranging from 97.13 ± 1.82 to 99.79 ± 1.91. The method is precise, reproducible, and complies with ICH guidelines, making it suitable for routine BSS drug analysis.
Summary
Source-checkedPlain-language reading of the full paper, prepared with AI and checked against the text. Each point links to the authors' own words.
Why it matters
- Bismuth subsalicylate (BSS) is a metallopharmaceutical drug used to treat gastrointestinal issues including diarrhea, nausea, heartburn, and indigestion. View evidence ↗
- Existing analytical methods for BSS, such as HPLC and spectrophotometry, are often limited by high costs, long analysis times, and a lack of sensitivity for trace-level detection. View evidence ↗
- Electroanalytical techniques like voltammetry provide a promising alternative due to their high sensitivity, selectivity, and minimal need for sample pretreatment. View evidence ↗
The question
- The study aims to develop and validate an electroanalytical method to quantify BSS in commercial pharmaceutical formulations. View evidence ↗
- The researchers also intend to investigate how different physicochemical conditions affect the redox behavior of BSS. View evidence ↗
What they did
- The experimental setup used a potentiostat with a glassy carbon electrode, a platinum auxiliary electrode, and an Ag/AgCl reference electrode, utilizing 0.04 M Britton-Robinson Buffer at pH 9.0. View evidence ↗
- The optimized cyclic voltammetry (CV) parameters were a scan rate of 0.05 V/s and a potential range from -0.1 to 1.5 V. View evidence ↗
- Linearity was evaluated using standard BSS solutions with concentrations ranging from 2 to 18 ppm. View evidence ↗
What they found
- The limit of detection (LOD) was 0.159 ppm and the limit of quantification (LOQ) was 0.4829 ppm, indicating high sensitivity. View evidence ↗
- The method showed high precision for a 12 ppm solution, with a relative standard deviation (%RSD) of 0.43% for intraday and 0.31% for interday measurements. View evidence ↗
- Accuracy studies showed recovery rates between 98.19% and 100.87%, confirming the method's accuracy. View evidence ↗
- When applied to commercial tablets (Bismatrol, Diotame, and Pepto Bismol), the mean content ranged from 97.13% to 99.79%, aligning closely with label claims. View evidence ↗
What it means
- The authors conclude that cyclic voltammetry is a simple, rapid, and effective method suitable for the routine quality control of bismuth subsalicylate. View evidence ↗
Visual summary
2 visualsIllustrations explain the paper; charts are replotted from the paper's own table values.
Electrochemical Setup
AI-generated conceptual illustration (A three-electrode electrochemical cell containing a glassy carbon electrode, a platinum wire, and a silver-silver-silver). It explains the idea and does not show study data.
View source evidence ↗
% Recovery: 6.0 vs 12.0 vs 18.0
Replotted from Table 2 (page 6) of the original paper. Every bar is the paper's own table value.
View source evidence ↗Figures & tables
From the original paper
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Table 1
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Table 2
Table 3
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Table 4Introduction
Bismuth subsalicylate (BSS), chemically known as basic bismuth salicylate, is an active pharmaceutical ingredient widely utilized for the treatment of gastrointestinal disorders such as diarrhea, indigestion, heartburn, and nausea [1][2][3] . As a non-systemic medication with antimicrobial and anti-inflammatory properties, BSS plays a vital role in managing infections such as Helicobacter pylori and acute diarrhea syndromes [4][5][6] . Despite its therapeutic importance, challenges persist in accurately and reliably quantifying BSS in pharmaceutical formulations due to its sparing solubility, complexation behavior, and hydrolysis in aqueous environments [7,8] . Traditional analytical approaches for BSS determination, including spectrophotometry, high-performance liquid chromatography (HPLC), atomic absorption spectroscopy, and gravimetric techniques, have been widely employed, but these often require extensive sample preparation, costly reagents, and lack the sensitivity required for trace-level quantification [9][10][11] . These limitations have stimulated interest in the development of alternative methodologies that are both rapid and cost-effective. Electroanalytical techniques such as voltammetry and polarography have emerged as powerful tools for pharmaceutical analysis, offering advantages such as high sensitivity, selectivity, low detection limits, and minimal sample pretreatment [12][13][14] . In particular, methods like cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV) have demonstrated considerable promise in the quantification of metal-containing drugs and complex organometallic compounds [15,16] . The electrochemical behavior of bismuth compounds is especially suited for such analysis due to their well-defined redox properties and affinity for ligand coordination [17] . Furthermore, regulatory authorities such as the International Conference on Harmonization (ICH) have emphasized the critical need for method validation in pharmaceutical quality control to ensure accuracy, precision, linearity, specificity, robustness, and reproducibility [18] . Therefore, validated electroanalytical methods are essential for routine quality assurance and regulatory compliance in pharmaceutical industries [19] . Given the pharmacological relevance of BSS and the necessity for robust analytical methods, the present study aims to develop and validate an electroanalytical method for the quantification of BSS in commercial formulations using differential pulse voltammetry. The study also seeks to explore the redox behavior of BSS under various physicochemical conditions, thereby providing a comprehensive understanding of its electrochemical profile. This approach offers potential for routine monitoring of BSS content in pharmaceutical preparations with greater speed, sensitivity, and operational simplicity [20] .
Electrochemical Analysis
Voltammograms of Bismuth Subsalicylate were recorded using cyclic voltammetry (CV) in unstirred solutions. Initially, blank voltammograms were obtained using the supporting electrolyte alone, following purging with nitrogen gas (99.9%) for 20 minutes to remove dissolved oxygen. Subsequently, the analyte solution was examined under identical experimental conditions. Prior to each measurement, the working electrode surface was carefully renewed and polished to ensure reproducibility and minimize contamination.
Method Optimization
Optimization of the cyclic voltammetry (CV) parameters for Bismuth Subsalicylate was performed using two different concentrations. Background voltammograms were first recorded under the following conditions:
A standard cyclic voltammetry procedure was employed, and the peak current (Ip) and peak potential (Ep) were
Ep was studied by varying one parameter at a time while keeping the others constant.
Effect of pH
The influence of pH (2-10) on Ip and Ep was studied using buffer solutions and supporting electrolytes. Graphs of Ip vs. pH and Ep vs. pH were plotted to evaluate pH-dependent electrochemical behavior.
After identifying the optimal pH, W K H H I I H F W R I V F D was examined in the range of 3-P 9 V 7 K H L Q I O X H scan rate on peak resolution and signal intensity was assessed while other parameters were held constant.
Repetitive Cycles
Using a 12-ppm solution of Bismuth Subsalicylate, repetitive CV cycles (4 cycles) were conducted at a scan rate
L were monitored to evaluate the electrochemical stability and adsorption behavior of the analyte.
Results and Discussions 3.1. Effect of Supporting Electrolytes
The choice of supporting electrolyte significantly influences the electrochemical response by affecting cell resistance and ion migration. The electrochemical behavior of Bismuth Subsalicylate was studied on a glassy carbon electrode (GCE) using cyclic voltammetry in various buffers (BRB, phosphate, acetate, carbonate; pH 1-10) and electrolytes
-Robinson buffer (BRB) at pH 9.0 provided the highest anodic peak current (Ipa = -q j $ D W ( S D -0.4560 V, indicating optimal sensitivity. Thus, BRB pH 9.0 was selected as the optimal supporting electrolyte for further studies.
Electrochemical characterization of BSS
The electrochemical characterization of Bismuth Subsalicylate (BSS) by cyclic voltammetry reveals a redox mec 1986). During the cathodic scan, a diffusion-controlled reduction peak appears due to the three-electron reduction of
% L h relationship between peak current and the square root of the scan rate (Bard and Faulkner, 2001). On the reverse scan, a corresponding anodic peak confirms partial reoxidation of
-OH group into a quinonoid-like structure (Ramirez-Silva et al ., 2004). This oxidation is pH-dependent, with peak potential shifting negatively with increasing pH, suggesting a proton-coupled electron transfer mechanism (Zhou
influence peak shape and position (Stumm and Morgan, 1996). These findings are consistent with standard electrochemical behavior reported in the literature for metalligand systems and support a dual redox mechanism for BSS. These processes are strongly influenced by pH, scan rate, and complexation, aligning with established electrochemical principles and published experimental data.
Effect of Solution pH
The electrochemical response of Bismuth Subsalicylate (BSS) was studied at a glassy carbon electrode in Britton-Robinson buffer (BRB) across pH 3-10. The peak current increased with rising pH, reaching a maximum at pH 9.0, which was chosen for further studies. The anodic peak potential (Epa) shifted linearly towards more negative values with increasing pH, suggesting proton involvement in the redox process as illustrated in Figure 2 and3. Linear regression equations were; Epa (V) = 0.037 -S + 5 0.9950) Epc (V) = 0.661 -S + 5 The
Method Validation 3.4.1. Linearity
The linearity of the developed electroanalytical method for the determination of bismuth subsalicylate was evaluated using cyclic voltammetry (CV). Standard solutions were prepared to obtain concentrations ranging from 2 to 18 ppm. For each concentration, cyclic voltammograms were recorded, and the anodic peak current was measured at a characteristic potential, as shown in Figure 4A. A gradual and consistent increase in anodic peak current was observed with rising concentrations of bismuth subsalicylate, indicating a strong linear relationship between analyte concentration and electrochemical response. To quantify this relationship, a calibration curve was constructed by plotting the anodic peak current on the y-axis against the concentration of bismuth subsalicylate (ppm) on the x-axis. The resulting plot, illustrated in Figure 4B, exhibited excellent linearity across the studied range. The linear regression equation obtained was y=0.470x+2.098, with a correlation coefficient (R †) of 0.997, confirming a strong correlation between current and concentration. These results demonstrate that the method provides a reliable, sensitive, and accurate electrochemical response across the tested concentration range, validating its effectiveness for quantitative analysis of bismuth subsalicylate.
Precision
The precision of the developed cyclic voltammetry (CV) method for the determination of bismuth subsalicylate was evaluated through both intraday (repeatability) and interday (intermediate precision) studies. For intraday precision, a 12 ppm solution of bismuth subsalicylate in BRB buffer (pH 9.0) was analyzed six times within a single day. The peak currents obtained were consistent, and the relative standard deviation (%RSD) was calculated to be 0.43%, indicating excellent repeatability. Interday precision was assessed by analyzing the same concentration over three different days by two different analysts as illustrated in figure 5. The resulting %RSD was 0.31%, which is well within the acceptable limit of less than 2%, confirming the high precision and reliability of the proposed CV method (Table 1).
| [BSS] (ppm) | Intraday precision Ipa (µA) | Interday precision Ipa (µA) | — | — | Average %RSD |
|---|---|---|---|---|---|
| Day 1 | Day 2 | Day 3 | |||
| 12.0 | 7.767 | 7.767 | 7.737 | 7.797 | 0.3100 |
| 12.0 | 7.797 | 7.797 | 7.787 | 7.758 | |
| 12.0 | 7.709 | 7.709 | 7.795 | 7.785 | |
| 12.0 | 7.747 | 7.747 | 7.777 | 7.759 | |
| 12.0 | 7.797 | 7.797 | 7.798 | 7.771 | |
| 12.0 | 7.759 | 7.759 | 7.764 | 7.787 | |
| %RSD | 0.4300 | 0.4300 | 0.3000 | 0.2100 |
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Accuracy
The accuracy of the proposed method was evaluated through recovery studies by spiking the sample with known amounts of pure bismuth subsalicylate. Solutions were prepared in triplicate at three concentration levels, and the percentage recovery was calculated using the regression equation derived from the calibration curve. The recovery data for bismuth subsalicylate is summarized in Table 2. The results show good recoveries in the range of 98.19-100.87 % using cyclic voltammetry (CV) indicating that method is accurate. However, the CV method was found to be more precise, as the relative standard deviation (%RSD) for both intraday and interday measurements was consistently below 2%, satisfying the precision criteria.
| Amount added (ppm) | Peak Current (µA) | Amount found (ppm) | % Recovery | % Recovery – SD (RDS) |
|---|---|---|---|---|
| 6.0 | 4.839 | 5.8319 | 97.199 | 98.191 – 1.3952 (1.42%) |
| 6.0 | 4.912 | 5.9872 | 99.787 | |
| 6.0 | 4.850 | 5.8553 | 97.589 | |
| 12.0 | 7.828 | 12.1915 | 101.596 | 100.87 – 0.9855 (0.977%) |
| 12.0 | 7.724 | 11.9702 | 99.7520 | |
| 12.0 | 7.810 | 12.1532 | 101.277 | |
| 18.0 | 10.63 | 18.1532 | 100.851 | 99.787 – 1.4526 (1.46%) |
| 18.0 | 10.59 | 18.0681 | 100.378 | |
| 18.0 | 10.40 | 17.6638 | 98.1320 |
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Limit of Detection and Limit of Quantification
The Limit of Detection (LOD) is the lowest concentration of analyte that can be reliably detected, while the Limit of Quantification (LOQ) is the lowest concentration that can be quantitatively determined with acceptable precision and accuracy. These parameters were calculated using the following equations LOD = (3.3 SD) / m LOQ = (10 SD) / m Where SD is the standard deviation of the y-intercept, and m is the slope of the calibration curve. For the cyclic voltammetry (CV) method, the LOD and LOQ were found to be 0.159 ppm and 0.4829 ppm, respectively. These values demonstrate the high sensitivity of the method, making it suitable for detecting and quantifying bismuth subsalicylate at low concentrations.
Robustness
The robustness of the developed method was evaluated by introducing small deliberate variations in experimental conditions, specifically by altering the buffer pH by -0.2%. These changes did not significantly affect the peak potential or peak current/absorbance, indicating that the method is reliable under minor fluctuations in analytical conditions. The details of the method validation summary are presented in Table 3.
| Parameter | Values | Parameter | Values |
|---|---|---|---|
| Absorption maximum / Anodic Peak potential | -0.005 V | Standard deviation | 0.0227 |
| Beer’s law range | 2-18 ppm | Accuracy (%) | 98.19-100.87% |
| Correlation coefficient | 0.997 | Precision (%RSD) | 1.13% |
| Regression equation | y = 0.470x + 2.098 | LOD (ppm) | 0.1590 |
| Slope | 0.470 | LOQ (ppm) | 0.4829 |
| Intercept | 2.098 | Solvent system pH | 9.0 |
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Application of Method
The developed electroanalytical method was applied for the quantitative determination of bismuth subsalicylate in commercially available fixed-dose tablet formulations.
Three marketed formulations containing bismuth subsalicylate were analyzed using the proposed method, and the results are summarized in Table 4. The bismuth subsalicylate content in each sample was calculated using the peak current values and the regression equations derived from the calibration curve. The mean assay values for all three products were found to be in close agreement with the labelled amounts, indicating the reliability and accuracy of the developed method. These results confirm that the method is suitable for routine quality control analysis of bismuth subsalicylate in fixed-dose formulations.
| Tablet Sample | Label Claim (mg) | Mean Content (%) – SD |
|---|---|---|
| Bismatrol | 262 mg | 99.79 – 1.91 |
| Diotame | 262 mg/15 ml | 98.46 – 2.11 |
| Pepto Bismol | 262 mg/15 ml | 97.13 – 1.82 |
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Conclusion
Cyclic voltammetry (CV) is a widely employed electroanalytical technique for investigating redox processes and elucidating electrode reaction mechanisms. In this study, CV was utilized for the qualitative and quantitative determination of bismuth subsalicylate, a metallopharmaceutical compound, in both standard solutions and pharmaceutical formulations. The compound exhibited a completely irreversible redox behavior at a glassy carbon electrode in Britton-Robinson Buffer (BRB). Optimized CV conditions included a scan rate of 0.05 V/s and a potential window ranging from -0.1 V to +1.5 V. The peak potential remained constant at approximately -0.005 V, indicating stable and reproducible electrochemical behavior. A linear calibration curve was obtained with a correlation coefficient (R †) of 0.997, demonstrating excellent linearity. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.1590 ppm and 0.4829 ppm, respectively. The procedure was validated in accordance with ICH guidelines for accuracy, precision, and robustness. Statistical evaluations confirmed the reliability and reproducibility of the method. Overall, cyclic voltammetry offers a simple, rapid, and highly effective analytical approach for the determination of bismuth subsalicylate, making it well-suited for routine quality control in pharmaceutical applications.
Figures and tables from the paper
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