Spectrophotometric Quantification of Telmisartan Employing Multivariate Calibration Technique in Bulk and Pharmaceutical Formulations

 

A. Sai Susmitha., Kokilambigai K. S*, Lakshmi K. S.

Department of Pharmaceutical Analysis, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur - 603203

 

ABSTRACT:

The present study focuses on the development and validation of an accurate, precise, sensitive and rapid multivariate calibration technique employing UV spectrophotometric method for the quantification of Telmisartan in bulk and pharmaceutical formulation. Multivariate calibration technique utilises the linear regression equations by correlating the relation between concentration and absorbance at five different wavelengths thereby improves the correlation and minimises the instrumental fluctuations. Telmisartan shows absorption maximum at 296 nm in alkaline condition, and good linearity was obtained in the range of 5 - 15 µg/mL. The other parameters were validated and were found to be following ICH guidelines.

 

 

 

INTRODUCTION:

Telmisartan, an angiotensin II receptor antagonist is used in the treatment of hypertension [1]. Telmisartan [Figure1] is chemically 4'- {[ 4- methyl - 6- (1- methyl - 1 H benzimidazole -2- yl) - 2 - propyl -1 H- benzimidazole -1 H- benzimidazole - 1- yl] methyl} - 2 - biphenyl - carboxylic acid. The molecular formula is C₃₃H₃₀N₄O₂ and has a molecular mass of 514.617 g/mol. It is presented as a white to off-white crystalline powder. It is essentially insoluble in water, sparingly soluble in strong acids and soluble in strong base [2,3]. The drug is official in IP, USP, BP [3,4,5].

 

Based on the detailed literature survey, the reported methods for quantification of Telmisartan includes spectrophotometric [6-22], HPLC [23-34], HPTLC [35,36], either in bulk, pharmaceutical formulations or in biological fluids as single or in combined dosage forms.

 

 

 

 

 

Figure 1 - Chemical structure of Telmisartan

 

Spectrophotometric methods because of their inherent rapidity, the simplicity of procedures and low cost, they are employed as a favorable method in most of the laboratories. The initiated protocol is based on the undeviating resolution of Telmisartan with an good degree of accuracy, linearity and precision. The process is simple, less cost and can be applied to vast medicaments and formulations. This article gives an account of using of UV spectral multivariate calibration method with uncomplicated mathematical content for the estimation of Telmisartan in a pharmaceutical dosage form.

 

Multivariate calibration stands for the conversion of common single species examining from one relying parameter to ‘m’ relying parameters. e.g. wavelengths or sensors, which can be concurrently incorporated in the calibration mode [37].

Under optimized conditions, the claimed statistical system furnishes significant resolving power, sensitivity, rapidity and is low expensive for the quantitative analysis, quality control and regular analysis of the investing combinations.

 

If the absorbance of an analyte (X) is measured at five wavelengths set (λ = 292, 294, 296, 298, 300nm), the following equation can be compiled for all selected wavelength.

A_λ292 = a X C_x + k₁…………………………………... (1)

A_λ294 = b X C_x + k₂…………………………………... (2)

A_λ296 = c X C_x + k₃…………………………………... (3)

A_λ298 = d X C_x + k₄ …………...................................... (4)

A_λ300 = e X C_x + k₅ …………….................................. (5)

 

Where A represents the absorbance of the analyte; a, b, c, d and e are the slopes of the linear regression responsibilities of the analyte; k_1, k_2, k_3, k_4, k₅ are the interrupts of the linear regression at the 5 specified wavelength and C_x stands for the concentration of the analyte. The above 5 equation systems (1-5) can be summarized as

 

A_T = a x C_x + b x C_x + c x C_x + d x C_x + e x C_x + K_T... (6)

Which can be simplified to

 

A_T = C_x (a+b+c+d+e) + K_T…(7),

 

Where A_T and K_T stands for the summation of the absorbance acquired and the summation of intercept of regression equations at 5 wavelengths fixed respectively. The concentration of the analyte X in a compound can be calculated by utilizing the equation.

 

 

 

 

MATERIAL AND METHODS:

Chemicals and solvents:

·         Distilled water

·         Sodium hydroxide

·         Analytical grade Telmisartan was obtained as gift sample from Orchid Pharma Ltd, Chennai. The marketed tablet formulation TELVAS (80 mg) was procured from the local market.

 

Instrumentation:

·         Perkin - Elmer UV- Visible double beam spectrophotometer

·         Sonicator

·         Electronic balance

 

Solubility studies:

Telmisartan was freely soluble in Sodium hydroxide. Hence 0.1 M sodium hydroxide was used as the solvent throughout the study.

Standard stock solution:

The standard stock solution containing 1 mg/mL telmisartan was prepared by dissolving 100 mg of telmisartan reference standard in 100 ml of 0.1 M sodium hydroxide. The solution is further diluted to get concentrations in the range of 5-15 µg/ mL.

 

Determination of λmax (Absorption maxima):

The standard stock solution of Telmisartan was diluted with the 0.1 M sodium hydroxide to obtain a concentration of 10 µg/mL solution. The mixture was subjected for scanning in the UV region from 200-400 nm, and the λmax was found to be 296 nm [Figure 2]. Now, to improve the correlation and reduce the instrumental oscillations, the absorbance of these solutions were investigated at selected wavelengths around the λmax 296 nm, i.e., 292, 294, 296, 298 and 300 nm.

 

 

Figure 2 - UV spectrum of Telmisartan showing λmax at 296 nm (10 µg/mL)

 

Preparation of sample solution:

Twenty tablets of Telmisartan was weighed, and those contents were transferred into a mortar, powdered and mixed well. A weight identical to 10 mg of Telmisartan was weighed accurately and dissolved in 10 mL of 0.1 M sodium hydroxide, sonicated, filtered and diluted for further analysis

 

Method validation:

The developed method was validated as per ICH Q2 R1 specifications for linearity, sensitivity, precision and accuracy[38].

 

Linearity:

The stock solution of Telmisartan was dissolved with the solvent to obtain concentrations in the province of 5-15 µg/ mL. Now to improve the correlation and reduce the instrumental oscillations, the absorbance of the above solutions were measured around the λmax of the drug (296 nm), i.e., 292, 294, 296, 298 and 300 nm. The corresponding absorbances at the selected wavelength for the above concentrations are shown in Table 1.

 

Table 1 - Multivariate UV calibration data at five selected wavelengths

Con (µg/mL)	Absorbance
	292 nm	294 nm	296 nm	298 nm	300 nm
5	0.269	0.271	0.273	0.269	0.264
6	0.331	0.332	0.334	0.324	0.320
7	0.369	0.373	0.385	0.369	0.361
8	0.419	0.421	0.437	0.418	0.410
9	0.47	0.472	0.481	0.468	0.459
10	0.519	0.521	0.539	0.516	0.509
11	0.579	0.591	0.608	0.598	0.569
12	0.634	0.644	0.645	0.638	0.619
13	0.688	0.7	0.702	0.695	0.678
14	0.731	0.735	0.751	0.732	0.725
15	0.781	0.789	0.794	0.785	0.769

 

Precision:

Intraday and interday precision was performed by replicate measurement of homogenous solution containing 5, 10 and 15 µg/mL for three times a day and for three days respectively at all five wavelength and the datas are shown in Table 2 and 3 respectively.

 

Table 2 - Intraday precision

Con (µg/ mL)	No. of Repetitions	Absorbance
		292 nm	294 nm	296 nm	298 nm	300 nm
5	1	0.269	0.271	0.273	0.269	0.264
	2	0.264	0.27	0.275	0.269	0.263
	3	0.269	0.271	0.273	0.267	0.260
10	1	0.514	0.521	0.523	0.516	0.503
	2	0.512	0.522	0.524	0.515	0.499
	3	0.512	0.52	0.525	0.516	0.503
15	1	0.781	0.789	0.794	0.785	0.769
	2	0.776	0.785	0.799	0.78	0.765
	3	0.783	0.785	0.805	0.781	0.770

 

 

 

Table 3 - Interday precision

Con (µg/ mL)	Day	Absorbance
		292 nm	294 nm	296 nm	298 nm	300 nm
5	1	0.268	0.27	0.274	0.27	0.264
	2	0.264	0.27	0.275	0.269	0.263
	3	0.269	0.271	0.273	0.267	0.260
10	1	0.515	0.52	0.523	0.512	0.503
	2	0.512	0.522	0.524	0.515	0.499
	3	0.512	0.52	0.525	0.516	0.503
15	1	0.781	0.789	0.794	0.785	0.769
	2	0.786	0.789	0.801	0.791	0.771
	3	0.783	0.785	0.805	0.781	0.772

 

Accuracy (Recovery studies):

Standard addition method was used to determine the accuracy of the method at 50%, 100%, 150%. From the prepared stock solution standard as well as test, 0.3 mL of standard solution was withdrawn into three volumetric flasks, and 0.2, 0.7, 1.2 mL of the sample solution was added to the earlier volumetric flasks, and the portion was made up to 10 mL with sodium hydroxide. The % recovery values were calculated.

 

Assay:

The absorbance of the extracted test mixture was reported at 296 nm, and the quantity of drug available in the formulation was estimated.

 

RESULTS AND DISCUSSION:

The advantages of multivariate calibration method reduces instrumental fluctuations by combining different measurements (e.g. light absorbance at several wavelengths). The λmax of Telmisartan was at 296 nm in 0.1M sodium hydroxide. All the calibration curves were linear across the concentration domain 5-15 µg/ mL. The linear regression calculation was found to be Y = 0.0524x + 0.0165 with R²=0.999. The percentage RSD for intraday precision and interday precision were found to be 0.1559 and 0.2095 respectively. The percentage recovery was within the prescribed limits. Hence all the parameters as per ICH guidelines were found to be well within the acceptance criteria.

 

Linearity:

The linearity for selected concentrations 5 - 15 µg/mL were recorded as shown in Figure 3, and the calibration curves at each wavelength are shown in Figure 4 - 8. The linearity data are provided in Table 4.

 

Precision:

The low value of SD at each wavelength indicates that the process was precise and the percentage RSD for intraday along with interday precision was in the range of 0.1120 - 1.0798, 0.1299 - 0.9909 respectively, which is well within the acceptance criteria of less than 2% at all wavelength. The low value of % RSD at all wavelength indicates that the procedure was precise and accurate. [Figure 9 and 10, Table 5 and 6].

 

 

 

Figure 3 - Overlay spectrum of Telmisartan showing linearity

 

 

Figure 4 - Calibration curve at 292 nm

 

 

Figure 5 - Calibration curve at 294 nm

 

 

Figure 6 - Calibration curve at 296 nm

 

 

Figure 7 - Calibration curve at 298 nm

 

 

 

Figure 8 - Calibration curve at 300 nm

 

Table 4 - Linearity data showing statistical parameters in absorbance mode

Wavelength (nm)	Regression equation	Slope	Intercept	% Intercept	R2
292	Y = 0.0514x + 0.0122	0.0514	0.0122	2.350	0.9990
294	Y = 0.0523x + 0.0092	0.0523	0.0092	1.765	0.9980
296	Y = 0.0524x + 0.0165	0.0524	0.0165	3.061	0.9986
298	Y = 0.0524x + 0.0047	0.0524	0.0047	0.910	0.9975
300	Y = 0.0511x + 0.0054	0.0511	0.0054	1.060	0.9990

 

 

Figure 9 - Overlay UV spectrum showing Intraday precision

 

 

Figure 10 - Overlay UV spectrum showing Interday precision

Table 5 - Intraday precision

Con (µg/ mL)	Description	292 nm	294 nm	296 nm	298 nm	300 nm
5	Mean	0.2673	0.2707	0.2737	0.2683	0.2623
	SD	0.0029	0.0006	0.0012	0.0012	0.0021
	% RSD	1.0798	0.2133	0.4219	0.4303	0.7935
10	Mean	0.5127	0.5210	0.5240	0.5157	0.5017
	SD	0.0012	0.0010	0.0010	0.0006	0.0023
	% RSD	0.2252	0.1919	0.1908	0.1120	0.4603
15	Mean	0.7800	0.7863	0.7993	0.7820	0.7680
	SD	0.0036	0.0023	0.0055	0.0026	0.0026
	% RSD	0.4623	0.2937	0.6890	0.3383	0.3445

 

Table 6 - Interday precision

Con (µg/mL)	Description	292 nm	294 nm	296 nm	298 nm	300 nm
5	Mean	0.2670	0.2703	0.2740	0.2687	0.2623
	SD	0.0026	0.0006	0.0010	0.0015	0.0021
	% RSD	0.9909	0.2136	0.3650	0.5686	0.7935
10	Mean	0.5130	0.5207	0.5240	0.5143	0.5017
	SD	0.0017	0.0012	0.0010	0.0021	0.0023
	% RSD	0.3376	0.2218	0.1908	0.4047	0.4603
15	Mean	0.7833	0.7877	0.8000	0.7857	0.7700
	SD	0.0025	0.0023	0.0056	0.0050	0.0010
	% RSD	0.3213	0.2932	0.6960	0.6406	0.1299

 

Recovery:

The % recovery of the drug from the synthetic mixture was found to be in the extent of 98.20 - 100.67 % w/w which falls properly inside the acceptance limit of 97-103% w/w as per the ICH recommendations as shown in Figure 11, Table 7.

 

 

Figure 11 - UV spectrum showing accuracy

Table 7 - Recovery studies

Wavelength (nm)	Amount present (µg/mL)	Amount added (µg/mL)	Absorbance	Amount Recovered (µg/mL)	% Recovery
292	3	2	0.269	4.978	99.27
		7	0.519	9.946	98.20
		12	0.781	14.994	99.80
294	3	2	0.271	4.989	99.63
		7	0.521	10.02	100.67
		12	0.789	14.987	99.57
296	3	2	0.273	4.969	98.97
		7	0.539	9.953	98.43
		12	0.794	14.987	99.57
298	3	2	0.269	4.998	99.93
		7	0.516	9.953	98.43
		12	0.785	14.959	98.63
300	3	2	0.264	5.016	100.53
		7	0.509	10.027	100.90
		12	0.769	14.985	99.50

 

Assay:

The absorbance of the extracted test mixture was reported at 296 nm, and the quantity of drug available in the formulation was estimated. The assay percentage of Telmisartan (Telvas tablets) was found to be 99.35 % w/w. The amount estimated in the formulation was found to be 79.47 mg, and the % RSD value was less than 2 % as represented in Table 8

 

Table 8 - Assay of Telmisartan

Label claim (mg)	Absorbance mode
	The amount estimated (mg)	% Assay
80	79.25	99.06
	79.89	99.86
	79.32	99.15
Average		99.35
SD		0.4388
% RSD		0.4416

 

CONCLUSION:

The currently developed spectrophotometric multivariate calibration method was validated by estimating diverse validation variables as per ICH guidelines and was found to be inside the recommended limits. The technique progressed in the present research was found to be sensitive, accurate, precise and reproducible for the specification of Telmisartan in its tablet formulation. Hence, this procedure is immensely convenient with understandable mathematical contents, and is more reliable than the alternative spectrophotometric methods and strongly proposed the developed method for routine analysis of Telmisartan in pharmaceutical formulations.

 

List of symbols/abbreviations:

nm = Nanometer

µg/mL = Microgram per millilitre

ICH = International Conference on Harmonization

UV = Ultraviolet

g/mol = Gram per Mole

IP = Indian Pharmacopoeia

USP = United States of Pharmacopoeia

BP = British Pharmacopoeia

HPLC = High Performance Liquid Chromatography

HPTLC = High Performance Thin Layer Chromatography

M = Molar

NaOH = Sodium hydroxide

 

CONFLICTS OF INTEREST:

Authors declare NO conflicts of interest.

 

ACKNOWLEDGEMENT:

Authors are thankful to The Chancellor, SRM Institute of Science and Technology, and SRM College of Pharmacy, SRMIST, Kattankulathur for providing various instruments and reprographic sources for carrying out this work.

 

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Received on 14.11.2018         Modified on 21.12.2018

Accepted on 18.01.2019         © RJPT All right reserved