Abstract
In this study, a simple, fast, and sensitive stability indicating CE method was developed for the quantification of Triamterene (TRM) and Hydrochlorothiazide (HCT) in pharmaceutical preparations. Detection was achieved using a photo diode array detector, and the separation process was conducted in a capillary with an inner diameter of 75 µm and a length of 40 cm. Optimum conditions were achieved by using a run buffer of 15 mM borate containing 20 mM SDS at pH 9.00, and applying a potential of 25 kV. HCT and TRM exhibited migration times of approximately 2.75 ± 0.007 min and 4.61 ± 0.022 min, respectively, under these conditions. The developed method was validated by assessing parameters such as linearity, selectivity, precision, accuracy, sensitivity, stability, and robustness. To assess the selectivity of the method, HCT, TRM, and tablets containing these compounds were exposed to acidic, basic, oxidative, thermal, and photolytic stress conditions. Ultimately, the method was proved successfully in accurately determining HCT and TRM levels in tablets.
Introduction
About 1.13 billion people worldwide are affected by systemic arterial hypertension (high blood pressure) [1]. The majority of hypertension patients are treated with thiazide diuretics [2]. Hydrochlorothiazide (HCT; 6chloro-3,4-dihydro-2H-1, 2,4 benzothiadiazine-7-sulphonamide1,1-dioxide) belongs to a class of thiazides that increases the excretion of sodium and water from the body [3]. Triamterene (TRM; 2,4,7-tri-amino-6- phenylpteridine) is of another medication belongs to potassium-sparing diuretics class that inhibits the exchange of sodium and potassium in the kidneys, preventing excessive potassium loss caused by other diuretics (Fig. 1) [4]. HCT and TRM are usually administered together to enhance treatment efficacy of hypertension [5].
Chemical structures. (a) HCT, (b) TRM
Citation: Acta Chromatographica 2025; 10.1556/1326.2025.01305
Analytical methods development for simultaneously determination of diuretics is important for several reasons such as safety monitoring for drug quality assessment and stress testing, treatment efficacy, dosing adjustment, and being prohibited substances by the World Anti-Doping Agency (WADA) (2004) for masking agents of doping [6].
For the simultaneous determination and quantitation of diuretics including HCT and TRM, high‐pressure liquid chromatography (HPLC) and high-performance thin layer chromatography (HPTLC) techniques have shown priority for analysis [7–10]. Despite the largely accepted techniques of HPLC, methods based on capillary electrophoresis (CE) have potential advantages superior to HPLC. The method offers high separation efficiency, requires only a small sample volume, minimizes sample matrix effects, and is highly versatile and flexible. It also benefits from well-established method validation and regulatory compliance, making it widely accepted in pharmaceutical analysis [11].
For the simultaneous determination of HCT and TRM, there are only a few studies which used spectrophotometry [12], LC [13, 14] electrochemical [15] and a CE method [16]. According to the literature review, no stability-indicating CE method has been specifically developed for TRM and HCT. In this study, a stability-indicating CE method was developed for the determination of HCT and TRM, and it was successfully applied for accurately determining HCT and TRM levels in tablet formulations.
Materials and methods
Reagent and solutions
HCT, TRM and all other analytical-grade chemicals were purchased from Sigma-Aldrich Additionally, the tablets including 25 mg HCT and 50 mg TRM (Trianseril®) were obtained from a local pharmacy in Turkey.
Equipment and conditions
Agilent G 7100A-DAD system (Agilent Technologies Deutschland, GmbH, Hewlett-Packard Waldbronn, Germany) was used for CE analyses. Capillary electrophoresis was carried out using a bare silica capillary with an inner diameter of 75 µm and an effective length of 40 cm (total length of 48.5 cm). For conditioning the capillary, it was initially washed with a 1 M sodium hydroxide solution for 30 min. Before each operation of the instrument, the capillary was washed with a 0.1 M sodium hydroxide solution for 10 min, followed by distilled water for 10 min, and then with the working buffer for 10 min. Between the analyses of samples, conditioning was performed by washing the capillary sequentially with a 0.1 M sodium hydroxide solution for 2 min, distilled water for 2 min, and the working buffer for 2 min. After daily usage of the instrument, the capillary was washed with a 0.1 M sodium hydroxide solution for 10 min and distilled water for 5 min, followed by purging with air for 2 min. Injections were performed under a pressure of 50 mbar for a duration of 10 s.
For the stability-indicating studies, we utilized a UV lamp (Vilber Lourmat, France), an ultrasonic bath sonicator (Sonorex, Germany), and an oven (Venticell, Germany). Photodegradation was conducted using a filtered medium-pressure mercury UV lamp at 254 nm with an irradiance level of 5 mW cm−2, providing a total radiation dose of 432 J cm−2 over 24 h at 25 °C ± 2 °C (room temperature).
Standard solutions and pharmaceutical dosage forms
Stock solutions of HCT and TRM were prepared in methanol (10−3 M) and stored in the dark at −18 °C. Working buffer diluted with water at a ratio of 1/10, was used as the dilution solvent. Trianseril® tablets containing 50 mg of TRM and 25 mg of HCT were used for the preparation of pharmaceutical dosage forms. Ten tablets were weighed, and the average tablet weight was determined (242.02 ± 0.24 mg). After grinding the tablets into powder, an amount equivalent to the average tablet weight was weighed. The weighed powder was then dissolved in methanol and mixed on a vortex mixer for 10 min. The tablet solution was kept in an ultrasonic bath for 10 min and then centrifuged at 4,000 rpm for 10 min. An appropriate amount of the supernatant was taken and diluted with a working buffer at a 1/10 ratio to match the calibration range. The solution was filtered through a 0.45 µm filter before analysis. The analysis was repeated six times, and the results were statistically evaluated.
Validation studies
The method was validated according to accuracy, precision, limit of detection (LOD), limit of quantification (LOQ), selectivity, robustness and specificity according to the ICH Q2 (R2) [17]. To assess the method's linearity, 11 different TRM solutions were prepared within the range of 2.62 × 10−8 to 1.24 × 10−5 M, and 11 HCT solutions were prepared in the range of 2.21 × 10−8 to 1.05 × 10−5 M. Precision was evaluated by analyzing TRM and HCT solutions with concentrations of 1.82 × 10−6 M and 1.53 × 10−6 M, respectively, for both intra-day and inter-day variability. Accuracy was demonstrated by analyzing TRM solutions at concentration levels of 5.46 × 10−7 M, 1.82 × 10−6 M, and 6.06 × 10−6 M, and HCT solutions at 4.60 × 10−7 M, 1.53 × 10−6 M, and 5.12 × 10−6 M, each analyzed six times for intra-day and inter-day precision. Sensitivity was determined by calculating the signal-to-noise (S/N) ratios. For the stability study, results from freshly prepared HCT and TRM solutions, each at an equal concentration of 2.0 × 10−6 M, were compared with those of solutions stored in the dark at −18 °C for 1 month and at +4 °C for 24 h. Robustness was evaluated by introducing minor changes in the optimal analysis conditions, and the effects on the results were examined and statistically compared with those obtained under optimal conditions. To demonstrate selectivity, both HCT and TRM standards (1.0 × 10−6 M), as well as their combination in the formulation, were subjected to various stress conditions, and analyses were repeated three times. The resulting electropherograms were reviewed for any interfering substances due to the applied stress conditions.
Results and discussion
Method development and optimization
The composition and concentration of the working buffer, pH value, organic solvent ratio, and applied potential parameters were investigated for the optimization of the CE method.
Analysis was performed using solutions of TRM and HCT at a concentration of 10−6 M for the optimization studies. Detection in the CE method was achieved using a DAD detector.
In the literature, it has been observed that different wavelengths (214–325 nm) have been used for the quantification of TRM and HCT in previous studies. Therefore, peaks obtained for both substances at wavelengths ranging from 210 to 325 nm were examined, and it was decided to use 225 nm for HCT and 230 nm for TRM in the analysis.
Initially, different buffers in the pH range of 3–9 were used to enable simultaneous analysis of HCT and TRM. Phosphate buffers at pH values of 3.0, 6.0, 7.0, and 8.0, acetate buffers at pH 4.0 and 5.0, and a borate buffer at pH 9.0 were prepared. The electropherograms obtained for a sample containing a mixture of HCT and TRM at these pH values.
While the peak of TRM was observed under acidic conditions, neither of the substances' peaks were observed under neutral conditions. Under basic conditions, only the peak of HCT was detected. Given this, it was considered that the addition of an anionic surfactant (SDS) to the working buffer could enable the detection of both substances. Preliminary experiments were conducted by adding SDS to the borate buffer in a basic environment, taking advantage of the contribution of electroosmosis to the separation. Successful separation was achieved in these preliminary experiments, and the study was based on this principle.
Buffer composition and concentration
In order to determine the buffer composition and concentration, initially, three borate buffers (pH 9.00) containing 10 mM, 20 mM, and 30 mM SDS were prepared. TRM and HCT solutions at a concentration of 10−6 M were analyzed three times at a potential of 27.5 kV. With the increase in buffer concentration, the analysis times also increased, along with an increase in the generated current. Based on the evaluations, it was decided to proceed with the study using a buffer containing 15 mM borate and 20 mM SDS.
pH
To investigate the impact of pH on the electrophoretic behavior of TRM and HCT, borate buffers containing 15 and 20 mM SDS with pH values of 8.50, 9.00, and 9.50 were tested. The analysis of TRM and HCT was performed three times using these three different buffers in CE. It was observed that when using the buffer with a pH of 9.50, the current increased significantly. Additionally, an adequate resolution (Rs) for the separation of the compounds could not be obtained at this pH. At pH 8.50, a reduction in the peak area of TRM and a closer proximity of HCT to the electroosmotic flow were observed. Based on these findings, a pH of 9.00 was selected as the working buffer.
Organic solvent
To enhance separation, the working buffer was prepared with varying concentrations of methanol as an organic solvent. Borate buffers at pH 9.00 were formulated with 20 mM SDS and 15 mM borate, containing 5%, 10%, and 15% (v/v) methanol, with three analyses conducted for each concentration. It was observed that increasing the amount of organic solvent in the working buffer resulted in a decrease in the Rs values to 9.8, 5.2, and 2.1 for 5%, 10%, and 15% (v/v) methanol, respectively, between the peaks. However, the lowest concentration of organic solvent did not significantly impact migration times but resulted in a reduction of peak areas. Consequently, it was decided to exclude the organic solvent from the working buffer.
Potential
The optimization of the applied potential, an instrumental parameter, was carried out for TRM and HCT using potentials of 22.5 kV, 25.0 kV, and 27.5 kV with a borate buffer (pH 9.00) containing 20 mM SDS and 15 mM borate. In CE, applying the highest possible potential facilitates faster separations. It was observed that as the potential increased, the analysis times decreased. However, to mitigate potential issues with Joule heating associated with high potentials, the study was conducted at 25.0 kV. This potential was determined to provide efficient separations while minimizing the risk of Joule heating problems.
Optimum conditions
Based on the parameters evaluated, the optimal conditions for analyzing TRM and HCT were established using a borate buffer (pH 9.00) containing 20 mM SDS and an applied potential of 25.0 kV. Under these conditions, the migration times for HCT and TRM were found to be 2.75 ± 0. 007 min and 4.61 ± 0.022 min, respectively (Fig. 2).
Electropherogram of HCT and TRM under optimum conditions
Citation: Acta Chromatographica 2025; 10.1556/1326.2025.01305
Validation of the methods
The separation methods developed were validated in accordance with ICH Q2 (R2) [17].
The developed method was validated by evaluating linearity, selectivity, precision, accuracy, sensitivity, stability, and robustness parameters. During the demonstration of method selectivity, various stress conditions were applied to determine whether the analytes were affected or not. Subsequently, the method was applied to pharmaceutical preparations containing TRM and HCT, and the results were evaluated statistically. AO values were used for calculations. Additionally, to demonstrate the suitability of the method, parameters such as number of theoretical plates (N), resolution factor (Rs), and asymmetry factor (As) were calculated.
Linearity
To investigate the linearity of the method, 11 different TRM solutions within the range of 2.62 × 10−8 – 1.24 × 10−5 M and 11 different HCT solutions within the range of 2.21 × 10−8 – 1.05 × 10−5 M were prepared. According to the statistical evaluation, it was determined that the method for TRM is linear in the range of 8.73 × 10−8 – 8.66 × 10−6 M and a linear equation (y = 211895x +0.006) with a high correlation coefficient (r = 0.9997) was obtained. It was determined that the method for HCT is linear in the range of 7.37 × 10−8 -7.32 × 10−6 M and a linear equation (y = 250334x + 0.004) with a high correlation coefficient (r = 0.9996) was obtained.
After determining the linear range, three sets of solutions were prepared at six different concentrations for TRM within the range of 2.18 × 10−7 – 8.66 × 10−6 M and for HCT within the range of 1.84 × 10−7 – 7.32 × 10−6 M. These solutions were analyzed for both intra-day and inter-day variations (Table 1).
Linearity, calibration and sensitivity data for the HCT and TRM
| HCT | TRM | |
| Linearity | ||
| Linearity range | 7.37 × 10−8–7.32 × 10−6 M | 8.73 × 10−8 – 8.66 × 10−6 M |
| Calibration | ||
| Slope | 250,334 | 211,895 |
| Intercept | 0.004 | 0.006 |
| Correlation coefficient (r) | 0.9996 | 0.9997 |
| Sensitivity | ||
| LOD | 3.23 × 10−9 M | 3.26 × 10−9 M |
| LOQ | 9.80 × 10−9 M | 9.90 × 10−9 M |
Precision
To demonstrate the precision of the method, TRM and HCT solutions with concentrations of 1.82 × 10−6 M and 1.53 × 10−6 M, respectively, were analyzed for intra-day and inter-day variability. Thus, it was demonstrated that the developed method has good precision and accuracy for the tested substances with %RSD values of <2% (Table 2).
Precision data for the HCT and TRM
| Intra Day | Interdays (n = 18) | |||||||
| Day I (n = 6) | Day II (n = 6) | Day III (n = 6) | ||||||
| TRM | HCT | TRM | HCT | TRM | HCT | TRM | HCT | |
| Mean | 0.391 | 0.390 | 0.389 | 0.398 | 0.378 | 0.391 | 0.386 | 0.393 |
| SD | 0.003 | 0.005 | 0.005 | 0.006 | 0.004 | 0.005 | 0.007 | 0.006 |
| RSD% | 0.809 | 1.412 | 1.357 | 1.643 | 1.261 | 1.444 | 1.861 | 1.655 |
| CI (%95) | ±0.015 | ±0.027 | ±0.026 | ±0.032 | ±0.023 | ±0.027 | ±0.053 | ±0.048 |
Accuracy
To demonstrate the accuracy of the developed method, TRM solutions at concentration levels of 5.46 × 10−7, 1.82 × 10−6, and 6.06 × 10−6 M, and HCT solutions at concentration levels of 4.60 × 10−7, 1.53 × 10−6, and 5.12 × 10−6 M were analyzed six times for intra-day and inter-day variability. The statistical evaluations resulted in recovery values ranging from 101.38% to 108.29% for all concentration levels of both substances (Table 3).
Accuracy data for the HCT and TRM
| Added (M) | Found (M) (Mean ± SD) | Recovery% | SE% | RSD% | ||
| Day I (n = 6) | TRM | 5.46 × 10−7 | 5.85 × 10−7 ± 1.06 × 10−8 | 107.23 | 7.23 | 1.81 |
| 1.82 × 10−6 | 1.87 × 10−6 ± 2.44 × 10−8 | 102.78 | 2.78 | 1.30 | ||
| 6.06 × 10−6 | 6.23 × 10−6 ± 6.23 × 10−8 | 102.84 | 2.84 | 0.99 | ||
| HCT | 4.60 × 10−7 | 4.68 × 10−7 ± 4.81 × 10−9 | 101.44 | 1.44 | 1.02 | |
| 1.53 × 10−6 | 1.61 × 10−6 ± 3.01 × 10−8 | 105.02 | 5.02 | 1.86 | ||
| 5.12 × 10−6 | 5.20 × 10−6 ± 6.19 × 10−8 | 101.60 | 1.60 | 1.18 | ||
| Day II (n = 6) | TRM | 5.46 × 10−7 | 5.82 × 10−7 ± 1.13 × 10−8 | 106.67 | 6.67 | 1.95 |
| 1.82 × 10−6 | 1.85 × 10−6 ± 3.26 × 10−8 | 102.07 | 2.07 | 1.75 | ||
| 6.06 × 10−6 | 6.26 × 10−6 ± 4.28 × 10−8 | 103.29 | 3.29 | 0.68 | ||
| HCT | 4.60 × 10−7 | 4.75 × 10−7 ± 7.82 × 10−9 | 103.06 | 3.06 | 1.64 | |
| 1.53 × 10−6 | 1.62 × 10−6 ± 2.51 × 10−8 | 105.33 | 5.33 | 1.54 | ||
| 5.12 × 10−6 | 5.24 × 10−6 ± 4.17 × 10−8 | 102.44 | 2.44 | 0.79 | ||
| Day III (n = 6) | TRM | 5.46 × 10−7 | 5.91 × 10−7 ± 3.59 × 10−9 | 108.29 | 8.29 | 0.60 |
| 1.82 × 10−6 | 1.84 × 10−6 ± 2.98 × 10−8 | 101.41 | 1.41 | 1.61 | ||
| 6.06 × 10−6 | 6.17 × 10−6 ± 6.83 × 10−8 | 101.79 | 1.79 | 1.10 | ||
| HCT | 4.60 × 10−7 | 4.82 × 10−7 ± 7.48 × 10−9 | 104.59 | 4.59 | 1.55 | |
| 1.53 × 10−6 | 1.58 × 10−6 ± 2.75 × 10−8 | 102.94 | 2.94 | 1.74 | ||
| 5.12 × 10−6 | 5.19 × 10−6 ± 6.49 × 10−8 | 101.38 | 1.38 | 1.24 | ||
| Interdays (n = 18) | TRM | 5.46 × 10−7 | 5.86 × 10−7 ± 9.44 × 10−9 | 107.40 | 7.40 | 1.61 |
| 1.82 × 10−6 | 1.85 × 10−6 ± 2.93 × 10−8 | 102.09 | 2.09 | 1.57 | ||
| 6.06 × 10−6 | 6.22 × 10−6 ± 6.76 × 10−8 | 102.64 | 2.64 | 1.08 | ||
| HCT | 4.60 × 10−7 | 4.75 × 10−7 ± 8.86 × 10−9 | 103.03 | 3.03 | 1.86 | |
| 1.53 × 10−6 | 1.60 × 10−6 ± 3.09 × 10−8 | 104.43 | 4.43 | 1.92 | ||
| 5.12 × 10−6 | 5.21 × 10−6 ± 5.87 × 10−8 | 101.81 | 1.81 | 1.12 |
Sensitivity
In order to determine the sensitivity of the study, calculations were performed using the S/N ratios. The LOQ values of the method for TRM and HCT were found to be 9.90 × 10−9 M (2.51 ng mL−1) and 9.80 × 10−9 M (2.91 ng mL−1), respectively. The LOD values in the method were calculated as 3.26 × 10−9 M (0.83 ng mL−1) for TRM and 3.23 × 10−9 M (0.96 ng mL−1) for HCT (Table 1).
Stability
For the stability study of the method, the analysis results of freshly prepared HCT and TRM solutions were compared with the analysis results of HCT and TRM solutions that were stored in the dark at −18 °C for 1 month and at +4 °C for 24 h. The calculated %RSD and % recovery values, along with the examination of the time interval, indicate that the HCT (%RSD = 0.81) and TRM (%RSD = 0.94) solutions were found to be stable.
Robustness
For the robustness study of the method, a solution containing 2 × 10−6 M TRM and HCT was analyzed under optimal conditions with slight variations. The modified conditions included buffer concentration, anionic surfactant concentration, and pH, with three experiments conducted for each condition. The results were statistically compared with those obtained under optimal conditions. The obtained %RSD values, which are found to be less than 2%, indicate that the small variations made in the method did not affect the results (HCT: %RSD = 0.66; TRM: %RSD = 0.78). Therefore, it can be concluded that the proposed method is robust and unaffected by minor changes.
Specificity
For specificity studies, blank matrix of pharmaceutical preparation were analyzed. No peak was observed in the analysis of pharmaceutical preparations (Fig. 3).
Electropherograms of all stress conditions applied to the tablet
Citation: Acta Chromatographica 2025; 10.1556/1326.2025.01305
Selectivity
To demonstrate the selectivity of the method, HCT and TRM standards, as well as their combination in the formulation, were subjected to various stress conditions. The analyses were repeated three times. The obtained electropherograms were examined to investigate the presence of any interfering substances due to the applied stress conditions. Additionally, the results were statistically evaluated in terms of HCT and TRM quantities. The applied stress conditions are presented in Table 4.
Applied stress conditions
| ACIDIC | BASIC | OXIDATIVE | THERMAL | PHOTOLYTIC | |
| HCT | 1 M HCl, 25 °C 60 min; 1 M HCl, 60 °C 60 min. | 1 M NaOH, 25 °C 60 min; 1 M NaOH, 60 °C 60 min. | %3 H2O2, 25 °C 60 min; %3 H2O2, 60 °C 60 min. | 60 °C oven, 60 min. | UV lamp, 24 h. |
| TRM | 1 M HCl, 25 °C 60 dk.; 1 M HCl, 60 °C 60 min. | 1 M NaOH, 25 °C 60 min; 1 M NaOH, 60 °C 60 min. | %3 H2O2, 25 °C 60 min; %3 H2O2, 60 °C 60 min. | 60 °C oven, 60 min. | UV lamp, 24 h. |
| TABLET | 1 M HCl, 60 °C 60 min. | 1 M NaOH, 60 °C 60 min. | %3 H2O2, 60 °C 60 min. | 60 °C oven, 60 min. | UV lamp, 24 h. |
It was observed that the peaks corresponding to HCT and TRM remained unaffected by the various stress conditions applied. However, in some instances, there were differences in the percentage amounts of the substances compared to the optimal conditions. Statistical evaluations of the degradation rates of the substances under different stress conditions are given in Table 5. The results indicated that the substances were most susceptible to degradation under photolytic conditions. The analysis of the tablets revealed that the highest level of degradation occurred under thermal stress conditions.
Quantities of HCT, TRM, and tablets under stress conditions
| Condition | % HCT | % TRM | % HCT (tablet) | % TRM (tablet) | %RSD HCT | %RSD TRM | %RSD HCT (tablet) | %RSD TRM (tablet) |
| Acidic (25 °C) | 95.88 | 64.03 | – | – | 0.98 | 0.78 | – | – |
| Acidic (60 °C) | 118.24 | 77.52 | 113.37 | 97.51 | 1.23 | 1.06 | 1.20 | 1.11 |
| Basic (25 °C) | 103.00 | 107.37 | – | – | 1.02 | 0.98 | – | – |
| Basic (60 °C) | 95.30 | 95.60 | 104.44 | 111.03 | 0.71 | 0.94 | 0.76 | 0.88 |
| Oxidative (25 °C) | 117.11 | 94.06 | – | – | 0.87 | 0.92 | – | – |
| Oxidative (60 °C) | 107.05 | 81.42 | 110.81 | 113.78 | 1.24 | 1.17 | 1.09 | 1.02 |
| Thermal (60 °C) | 117.02 | 104.81 | 27.61 | 13.42 | 1.03 | 0.83 | 1.38 | 1.41 |
| Photolytic | 12.26 | 16.02 | 98.50 | 99.25 | 1.28 | 1.19 | 0.79 | 0.86 |
Afterwards, the degradation profiles of HCT and TRM in tablets were examined, similar to the standard solutions. Figure 3 presents a comparison of the electropherograms obtained under the stress conditions applied to the tablet with an electropherogram obtained under optimal conditions.
System suitability tests
The system suitability parameters of the developed method were evaluated, and the results demonstrate that the method complies with the acceptance criteria for the substances, confirming its suitability.
Tablet assays
The tablet analyses were performed to obtain electropherograms that exhibit peak characteristics of the standard substances used in the developed CE method. Figure 4 presents an electropherogram corresponding to one of these analyses.
Electropherogram of blank and tablet analysis containing TRM and HCT
Citation: Acta Chromatographica 2025; 10.1556/1326.2025.01305
Statistical evaluations for the quantification of TRM and HCT from tablets using the CE method are presented in Table 6.
Quantitative determination data for TRM and HCT tablets
| TRM | Mean (n = 6) | 50.16 mg |
| SD | 0.72 | |
| RSD% | 0.71 | |
| Recovery% | 100.52 | |
| HCT | Mean (n = 6) | 25.29 mg |
| SD | 0.90 | |
| RSD% | 0.89 | |
| Recovery% | 101.14 |
The evaluations showed that the percent recovery values were approximately at the level of 100%. This indicates that the developed CE method can be used for the quantification of TRM and HCT from tablets.
Conclusions
In this study, a simple, fast, and sensitive CE method has been developed for the quantitative determination of TRM and HCT in pharmaceutical preparations. The selectivity parameter of the method has been validated to include various stress conditions, and its applicability for analysis of tablets has been demonstrated. A literature review revealed the absence of a stability-indicating CE method specifically developed for TRM and HCT, making the proposed method a valuable contribution to the field. The developed method is recommended for the individual and simultaneous determination of TRM and HCT due to its simplicity, affordability, sensitivity, and speed. Furthermore, it is believed that the proposed methods could serve as a foundation for the determination of TRM and HCT in various biological fluids. Therefore, it is believed that the method proposed here will contribute to the literature in this regard.
Author contributions
Concept and Design: SDC, AGDP. Contributed analysis tools: SDC, AGDP. Performed analysis: SDC, AGDP. Analyzed and Interpreted: SDC, AGDP. Wrote the paper: SDC, AGDP.
Conflict of interest
The authors have no conflict of interest.
Acknowledgments
This study was supported by Anadolu University Scientific Research Projects Commission under the grant no: 1808S279.
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