Development of Ion- pair Extractive Spectrophotometric Method for the determination of Ranolazine in Pharmaceutical Dosage Forms

Jitendra Yadav*, Prashant Kumar Sahu, Jayesh Verma, Ashutosh Kumar Singh,

Aakanksha Sinha, Sanjay J. Daharwal

University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G.), Chhattisgarh, India.

*Corresponding Author E-mail: jy7288096@gmail.com, daharwalresearch@rediffmail.com

ABSTRACT:

A validated ion- pair extractive spectrophotometric method was developed for the quantitative determination of ranolazine in bulk drug and tablet dosage forms. These methods are based on stable colored ion-pair spectrophotometric method between Ranolazine and acidic dyes in acidic medium, followed by extraction into chloroform. The absorbance of the extracted chromogen was measured at 418nm respectively. The proposed methods were validated statistically. Recoveries of methods were carried out by standard addition methods. For the Bromophenol green dyes, the calibration curve showed good linearity in the concentration range of 40-90 µg/ml with a correlation coefficient (R²) of 0.995 for UV spectrophotometric measurements. Similarly for the Bromophenol blue dyes, linearity was observed in the concentration ranges of 40-90 µg/ml with R² 0.998for UV spectrophotometric measurements indicating good linearity. The low standard deviation and % RSD values obtained for both Bromocresol green dyes and Bromophenol blue dyes indicate good repeatability and precision of this method. Both colorimetric and UV- spectrophotometric reading showed %RSD within acceptable limits, confirming the reliability of the measurements.

KEYWORDS: Colorimetric, Bromophenol blue, Bromocresol green and UV-VIS Spectrophotometric and %RSD.

1. INTRODUCTION:

Ranolazine is a novel anti-anginal medication widely used in the management of chronic stable angina. It is N-(2,6- dimethylphenyl)-2-[4-[2-hydroxy-3-(2-methoxyphenoxy) propyl] piperazin-1-yl] acetamide.¹ Anti-anginal drugs reduce oxygen demand, increase myocardial oxygen supply, or both to alleviate severe myocardial ischemia. Nitrates, β-adrenoceptor antagonists, and calcium channel blockers are the three primary pharmacological classes that effectively reduce the incidence and intensity of angina. Knowledge of the equilibrium between myocardial oxygen supply and demand is necessary to comprehend the advantageous effects of these agents.² A white to off-white solid, ranolazine dissolves readily in methanol and dichloromethane. It is poorly soluble in water and only slightly soluble in ethanol, acetonitrile, acetone, tetrahydrofuran, ethyl acetate, isopropanol, toluene, and ether.³ in rabbits with myocardial ischemia, ranolazine affects late sodium current and sodium-dependent calcium channels.⁴

By inhibiting late sodium channels and limiting intracellular calcium overload, ranolazine lowers myocardial oxygen demand and angina symptoms without appreciably altering blood pressure or heart rate. For individuals with refractory angina who are not responding to conventional medications, its distinct activity in cardiac myocytes makes it superior to other second-line medicines like nicorandil or ivabradine.⁵ Without lowering blood pressure or heart rate, ranolazine has anti-ischemic and anti-anginal properties. By lowering the late sodium current, it is anticipated to decrease sodium inflow into ischemic myocardial cells. This may indirectly reduce calcium uptake through the sodium/calcium exchanger. For patients who do not respond well to other anti-anginal drugs, ranolazine may be taken in addition.^6,7

Spectrophotometric techniques, like absorbance and area under the curve (AUC) measurements, are highly valued for their adaptability, simplicity, and cost-effectiveness in analysis. UV/Visible spectrophotometers are widely available instruments that can be used by research labs and pharmaceutical firms to suit their analytical needs. These devices are a practical and cost-effective alternative to more complex systems like HPLC⁸, RP-HPLC⁹, RP-UPLC¹⁰, HPLC-UV¹¹, LC¹², LC-MS¹³, Analytical reports provide a number of spectrophotometric approaches, including absorbance¹⁴, derivative¹⁵, and differential spectrophotometry, for the simultaneous measurement of Ranitidine hydrochloride (RAN.HCl) and Metformin hydrochloride (MET)¹⁶. Furthermore, the estimation of Ranolazine with Dronederone and the simultaneous measurement of RAN.HCl with Metoprolol have been discussed.¹⁷

Figure 1: Structure of Ranolazine

2. EXPERIMENT:

2.1 Instrument:

A single beam SYSTRONIC UV-VIS spectrophotometer model-117 was used as instrument. The absorption spectra of the test and reference solutions were recorded between 200 and 400nm while they were stored in 1cm quartz cells. Digital Photoelectric Colorimeter used to measure the heat change associated with chemical, physical, or biological processes and model-113.

2.2 Chemicals and Reagents:

Methanol (Merck Pvt. Ltd. India), several dyes were tested, out of which only Bromocresol green (Fisher Scientific) and Bromophenol blue (Molychem) gave satisfactory results and were selected. Different buffer systems were evaluated during this analytical method development. Among them phosphate buffer (PH-3) was selected as it showed better solubility, stable absorbance and good reproducibility.

2.3 Pharmaceutical matrices:

Ranolazine 500mg is found in Renolzin-500 SR (Ranolazine sustained release tablets), which are produced in India and sold by Knoll Healthcare Pvt. Ltd.

2.4 Preparation of standard stock solutions and working solution:

The standard stock solutions (1mg/ml-1000µg/ml) and working solutions (0.1mg/ml= 100µg/ml) of Ranolazine was prepared in methanol. Take 100mg of Ranolazine in 100ml volumetric flask and make up volume to 100ml with methanol (Stock solution). Pipette out 10ml from stock solution into a 100ml volumetric flask and then make up the volume with methanol.

2.5 Preparation of Buffer solution:

In accordance with the Indian Pharmacopoeia, phosphate buffer (PH-3.0) was created by combining a suitable volume of 0.2M phosphate solution and 0.2M hydrochloric acid. The final volume was then increased to 200ml using distilled water.

2.6 Linearity for the spectrophotometric methods:

Aliquot portion of the 0.1mg/ml Ranolazine working solution (4, 5, 6, 7, 8, and 9ml) were precisely transferred to 10ml volumetric flasks; methanol were used to make up the volume. All the solutions are used in this method and absorbance show in 418nm.

2.7 Analysis of commercial tablet formulation:

Accurately weigh and finely powder twenty tablets. Transfer a quantity of the powdered material equivalent to 0.138g of Ranolazine ( equivalent to 0.100g as per its equivalent weight and make up the volume in 100ml volumetric flask with methanol (Solution-A). The solution is to be filtered and 10ml is to be taken and volume is to be made up in a 100ml volumetric flask with methanol. Measure the absorbance of the resulting solution (Solution-B) at 418nm.

3. METHODOLOGY:

3.1 Method -I (Bromophenol blue):

A series of separating funnels were used to pipette out an appropriate amount of the working standard pharmaceutical solutions. 10 of pH 3.0 buffer and 5ml of Bromophenol blue were added to each funnel. 10ml of chloroform were added to each funnel. After shaking the solutions to thoroughly mix the two stages, they were let to stand for five minutes to ensure that the layers were clearly separated. At the wavelength of the maximum absorbance (λ max 418nm), the absorbance values of the chloroform layers were measured against the corresponding reagent blank.

3.2 Method –II (Bromocresol green):

A series of separating funnels were used to pipette out an appropriate amount of the working standard pharmaceutical solutions. 10 of pH 3.0 buffer and 5ml of Bromocresol green were added to each funnel. 10ml of chloroform were added to each funnel. After shaking the solutions to thoroughly mix the two stages, they were let to stand for 5minutes to ensure that the layers were clearly separated. At the wavelength of the maximum absorbance (λ max 418nm), the absorbance values of the chloroform layers were measured against the corresponding reagent blank.

4. RESULT AND DISCUSSION:

The proposed ion pair extractive spectrophotometric method effectively determines ranolazine in tablet forms by forming a stable-colored ion pair complex with an acidic dye showing in figure-1. After the complex is extracted into chloroform, a transparent solution is produced for spectrophotometric analysis.

Buffer solution PH, Dye concentration, chloroform volume and shaking time and reagent addition order were among the parameters that were optimized to improve color intensity and repeatability. This method follows to Beer Lambert’s law within the selected concentration range and showing excellent linearity with a good correlation coefficient.¹⁸

Ranolazine can create stable ion-pair complexes with acidic dyes in acidic surroundings, which aid in the selective extraction of these complexes into chloroform and lessen tablet excipient interference. The optimization of the approach yields accurate findings (%RSD values) and recovery rates, improving the stability and absorbance of the colored complex. The UV spectrum of the drug showed maximum absorbance at 418 nm for Bromocresol Green and Bromophenol Blue (Figure-3). The calibration curve was found to be linear in the range of 40-90mg /ml for Method-I and II (Figure-4).

Overall, the developed ion-pair extractive spectrophotometric method is simple, rapid, sensitive, economical and accurate, and can be effectively applied for routine quality control analysis of ranolazine in pharmaceutical tablet dosage forms.

Figure 2: Experiment setup and color development during analysis

Table 1: Absorbance values obtained by UV-VIS Spectrophotometric methods (n-3)

S. No	Concentration of ranolazine drug (mg /ml)	Bromophenol blue		Bromocresol green
S. No	Concentration of ranolazine drug (mg /ml)	Absorbance reading (λ max-418)	Molar Absorptivity	Absorbance reading (λ max-418)	Molar Absorptivity
1	40 mg /ml	0.173	0.004325	0.301	0.007525
2	50 mg /ml	0.203	0.00406	0.360	0.0072
3	60 mg /ml	0.234	0.0039	0.415	0.00691
4	70 mg /ml	0.280	0.004	0.489	0.0069857
5	80 mg /ml	0.326	0.004075	0.559	0.0069875
6	90 mg /ml	0.365	0.00405	0.602	0.006688
Molar Absorptivity mean		0.004068		0.007049

5. CONCLUSION:

The developed ion-pair extractive spectrophotometric method is simple, rapid, sensitive, economical and accurate, and can be effectively for analysis of ranolazine in pharmaceutical tablet dosage forms. The acceptable % recovery values attained using the suggested technique show that common excipients found in the ranolazine tablet formulation do not interact. The low standard deviation and %RSD values confirm the good reproducibility, repeatability and accuracy of the developed methods. These results clearly demonstrate the reliability of the ion pair extractive spectrophotometric methods. These methods are based on the direct formation of stable colored ion- pair chromogen between ranolazine and acidic dyes. The stability of the chromogen and efficient extraction into chloroform contribute to consistent absorbance measurements and improved selectivity of the method for ranolazine.

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Received on 07.12.2025 Revised on 24.01.2026

Accepted on 12.03.2026 Published on 16.04.2026

Available online from April 18, 2026

Asian Journal of Pharmaceutical Analysis. 2026; 16(2):160-164.

DOI: 10.52711/2231-5675.2026.00024

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Parameter	Bromophenol blue UV-VIS spectrophotometer	Bromocresol green UV-VIS spectrophotometer
Linearity plot range (mg/ml ^*and µg/ml)	40-90 µg/ml	40-90 µg/ml
Slope	0.002	0.003
intercept	0.002	0.008
Correlation coefficient	0.997	0.996

Amount of Sample Added in (µg/ml)	Amount of Standard Added in (µg/ml)	Percentage recovery (%)	Standard deviation	Percentage of relative standard deviation
40	20	100.8523	0.426505	0.42290062
40	40	101.021	0.469716	0.4696738
			Mean:0.4481105	Mean: 0.4462721

Amount of Sample Added in (µg/ml)	Amount of Standard Added in (µg/ml)	Percentage recovery (%)	Standard deviation	Percentage of relative standard deviation
40	20	100.7167	0.965004	0.95813703
40	40	100.3559	0.471195	0.46952396
			Mean: 0.7180995	Mean: 0.713830495