Development and Validation of UV Spectroscopic method for the determination of Sonidegib in Bulk and Pharmaceutical dosage form

 

Murugan S1,2*, Vetrichelvan T1

1Department of Pharmaceutical Analysis, Adhiparasakthi College of Pharmacy, Melmaruvathur-603319, Tamilnadu, India.

2Research Scholar, The Tamilnadu Dr. M.G.R. Medical University, Chennai-600032, Tamilnadu, India.

*Corresponding Author E-mail: msm_apcp07@yahoo.com

 

ABSTRACT:

Two simple UV method was developed for the determination of sonidegib in bulk and pharmaceutical dosage form. The method involves the Zero and First order derivative. Sonidegib has λmax 277nm in zero order. In first order the wavelength selected was 293nm. The methods were found to be linear between the range of 3–15µg/ml for Sonidegib in methanol. The Zero and First-order derivative methods shows good linearity in the above concentration range and correlation coefficient is 0.9994 and 0.9998, respectively.

 

KEYWORDS: Sonidegib, UV Method, Zero order, First order.

 

 

INTRODUCTION:

Sonidegib (Figure 1), chemically N-[6-(cis-2,6-dimethylmorpholin-4-yl) pyridin-3-yl]-2-methyl-4'-(trifluoromethoxy) [1,1'-biphenyl]-3-carboxamide [1]. It inhibit activation of the Hedgehog pathway. Sonidegib is primarily metabolized by CYP3A and is eliminated hepatically [2].

 

Fig. 1 Chemical structure of Sonidegib [3]

 

On literature survey, No method was reported for the estimation of Sonidegib. So we have developed a novel, simple, rapid, accurate, precise, economical and highly sensitive UV spectrophotometric methods for assay of Sonidegib in bulk form according to ICH guidelines. The developed method was validated as per ICH norms [4-5].

 

MATERIALS AND METHODS:

Instrumentation:

The instrument used in the present study was Shimadzu double beam UV/Visible spectrophotometer (Model UV- 1700) with spectral band width of 1 nm. All weighing was done on electronic balance (Model Shimadzu AUX -220).

 

Reagents and Chemicals:

Analytically pure sample of Sonidegib was supplied by Beijing mesochem technology co.ltd. (China). The pharmaceutical dosage form used in this study was Odomzo capsule contains equivalent to 200mg of Sonidegib per capsule.

 

Preparation of stock standard solution:

Standard stock solution of Sonidegib (2000𝜇g/ml) was prepared by dissolving 200mg Sonidegib in 100ml of Methanol in 100ml volumetric flask with vigorous shaking. From this stock solution, 1.5ml was withdrawn and diluted to 100ml using methanol to get working concentration of 30𝜇g/ml.

 

Methods:

Method 1: Zero order method:

In this method, solution of Sonidegib (10μg/ml, each), was prepared by appropriate dilution of standard stock solution with Methanol and scanned in the spectrum mode from 400nm to 200nm. From the spectra of this drug, wavelength selected for quantitation was 277nm for Sonidegib. The spectra of Sonidegib is shown in Fig.No.2.

 

Fig. 2 The absorption spectra of Sonidegib

 

Method 2: First order derivative method:

In this method, solution of Sonidegib (10μg/ml), was prepared by appropriate dilution of standard stock solution with Methanol and scanned in the spectrum mode from 400nm to 200nm. The absorption spectra thus obtained were derivatized for first order. From the first spectra of this drug, wavelength selected for quantitation were 293nm for Sonidegib The first order derivative spectra of Sonidegib is shown in Fig.No.3.

 

Fig. 3 The first order derivative spectra of Sonidegib

 

Analysis of Marketed Capsule Formulation:

For the estimation of drugs in commercial formulations, twenty capsules containing 200mg of Sonidegib was weighed and average weight was calculated. An accurately weighed portion of powder sample equivalent to 200mg was transferred into a 100ml clean dry volumetric flask containing 70mL of methanol. The contents of the flask were sonicated for 10 min and the volume was made up to the mark with a further quantity of the methanol to get a stock concentration of Sonidegib. Further pipette 1.5ml of the above stock solution into a 100mL volumetric flask and the volume was made up to the mark with the methanol. Then, 2ml was withdrawn and diluted to 10mL using methanol to get 6𝜇g/ml of Sonidegib, the concentration of Sonidegib was determined by measuring absorbance of sample solution in zero and first order derivative by using 277 nm and 293nm, respectively. Concentration of Sonidegib in the diluted solution was obtained from calibration curves. Amount of Sonidegib in mg/cap was then calculated, by multiplying the concentration obtained with dilution factor.

 

Validation:

The proposed methods were validated as per ICH guidelines.

 

Linearity:

Different aliquots of 1.0-5.0ml of Sonidegib was transferred into series of 10ml volumetric flasks, separately and the volume was made up to the mark with Methanol to get concentrations 3, 6, 9, 12 and 15μg/ml, respectively. The absorption spectrum was recorded at 277nm in zero order derivative. The absorption spectrum were derivatized to get first order and recorded the absorbance in first order at 293nm.

 

Accuracy:

To the preanalysed sample solutions, a known amount of standard stock solution was added at different levels i.e. 50, 100 and 150%. The solutions were reanalyzed by proposed method.

 

Precision:

The reproducibility of this methods was determined by analyzing capsules at different time intervals on same day in triplicates (Intra-day assay precision) and on three different days (Inter-day assay precision).

 

RESULT AND DISCUSSION:

The methods discussed in the present work provide a convenient and reliable way for quantitative determination of Sonidegib in capsule formulation. The wavelength selected for zero order was 277nm. In first order, the wavelength selected was 293nm. Percent label claim for Sonidegib in capsule analysis was found to be 99.48% in zero order and 100.88% in first order derivative method as shown in Table 1. Percent recovery for Sonidegib, was found to be 99.96% in zero order and 100.35% in first order derivative with standard deviation well below 2 indicating accuracy of this methods as shown in Table 2. Intra-day and Inter-day precision studies were carried out by analyzing capsule formulation, three times on the same day and on three different days, respectively. Standard deviation and coefficient of variance for intra-day and inter-day precision studies was satisfactorily low indicating high degree of precision and reproducibility of this methods.

 

Table 1. Results of Analysis of Capsules

Capsule sample

Label claim (mg/cap)

% Label claim (n = 6)

%RSD

Method 1

Method 2

Method 1

Method 2

Formulation

 200

99.48

100.88

0.8438

0.7539

 

Table 2. Results of Recovery Studies for formulation

Recovery level

Initial amount (𝜇g/mL)

Concentration of std drug added (𝜇g/mL)

% Recovery (𝑛 = 3)

 

 

 

Method 1

Method 2

50%

6.0

3.0

99.64

100.54

100%

6.0

6.0

99.48

99.87

150%

6.0

9.0

100.76

100.66

 Mean

99.96

100.35

 

CONCLUSION:

The proposed UV spectrophotometric methods employed here proved to be simple, economical, rapid, precise and accurate. Thus these can be used for routine estimation of Sonidegib in capsule dosage form.

 

ACKNOWLEDGMENT:

The management of ACMEC trust is hereby thanked by one of the author Mr. S. Murugan for their support in doing this research.

 

REFERENCE:

1.      https://www.drugbank.ca/drugs/DB09143

2.      https://en.wikipedia.org/wiki/Sonidegib

3.      https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:90863

4.      Code Q2A – Text on Validation of Analytical Procedure Methodology Step-3 Consensus Guideline, ICH Harmonised Tripartite Guideline, 2005.

5.      Code Q2B – Text on Validation of Analytical Procedure Methodology Step-3 Consensus Guideline, ICH Harmonised Tripartite Guideline, 1994.

 

 

 

 

Received on 16.10.2019           Modified on 25.12.2019

Accepted on 04.03.2020         © RJPT All right reserved

Research J. Pharm. and Tech. 2020; 13(10):4836-4838.

DOI: 10.5958/0974-360X.2020.00851.3