INTRODUCTION:

Vortioxetine hydrochloride is chemically 1-[2-(2,4-dimethylphenyl) sulfanyl phenyl] piperazine; hydrochloride is an orally administered antidepressant for the treatment of major depressive disorders¹, and its chemical structure is shown below. Vortioxetine hydrochloride has been shown to improve human cognitive functioning. The antidepressant effect of Vortioxetine hydrochloride was demonstrated through a "multi-modal" mechanism of action. It is an antagonist for 5-HT1A receptors and antagonist for 5-HT3A,5-HT7 receptors and inhibits serotonin transport through specific serotonin transporters.^2-5. Several analytical methods like RP-HPLC, UPLC-MS/MS, HILIC-MS have been developed reported for estimation of vortioxetine hydrochloride in bulk, pharmaceutical dosage form, human plasma and rat plasma.^6-10 Similar methods for other drugs are also reported.^11-25

Structure of Vortioxetine Hydrochloride

The majorities of existing methods are costly, time consuming, inconvenient, and necessitate the use of highly skilled operating employees. There are no UV spectrophotometric methods for estimating vortioxetine HCL in bulk and vortioxetine hydrochloride estimate requires simple and specific UV spectrophotometric procedures. UV spectrophotometry is widely utilised for assessment of medicinal substances used as pharmaceuticals due to its speed, simplicity, and reproducibility, as well as the fact that it requires a minimal solvent system and analysis time. Due to these current goals of work, simple, sensitive, and selective UV spectrophotometric techniques for vortioxetine hydrochloride in bulk and pharmaceutical dose forms are being developed and validated. The goal of this work was to develop cost-effective, simple, and selective UV spectrophotometric procedures employing methanol as a diluent. The procedures were adjusted and verified in accordance with ICH criteria, and vortioxetine hydrochloride was found to have high specificity, linearity, precision, and accuracy.

MATERIALS AND METHODS:

Materials:

The study was carried out by using Shimadzu UV spectrophotometer Spectronic model 1800 with 1cm matched quartz sample cells. Single Pan Electronic balance was used for weighing purpose; Calibrated volumetric glassware was used for the validation study. Vortioxetine Hydrochloride standard was obtained as gift sample from Apotex Research Limited Bangalore. All reagents used were of analytical grade, Brintellix (10mg of vortioxetine hydrochloride) tablets purchased from local commercial sources. All chemicals or solvents (methanol) were analytical and was used to prepare solutions wherever required.

a) Methodology for the determination of maximum wavelength:

50mg of Vortioxetine Hydrochloride was weighed accurately and transferred into a 50ml vol, flask and dissolved in 50ml of Methanol and made up to volume with the same Methanol solvent to give a standard concentration of 1000μg/ml, transfer 5ml of the above solution into 50ml vol. Flask dilute and made up to volume with the Methanol solvent to make 100µg/ml. This solution was scanned against blank for the entire UV-visible wavelength 200-400nm. Based on the spectrum λ max of 230nm was selected for further analysis.

b) Preparation of standard stock solution:

The standard stock solution was prepared by transferring accurately weighed 50mg of pure vortioxetine hydrochloride into a 50ml volumetric flask and then 50 ml methanol was transferred into volumetric flask and dissolved. The volume was made up to the mark with methanol which gives solution containing 1000µg/ml Vortioxetine Hydrochloride.From this solution 5ml was transfer to 50ml volumetric flask to this solution 50ml methanol was added to give a solution containing 100 µg/ml of Vortioxetine Hydrochloride.

c) Preparation of Serial dilutions:

Stock solution of 100μg/ml of Vortioxetine Hydrochloride was prepared in Methanol, for First Order Derivative spectrophotometric analysis. The dilutions were obtained by pouring 5, 10, 15, 20, 25ml of a 100µg/ml concentration into a 50ml volumetric flask. Topping up with methanol to achieve the target level. The concentration are 10, 20, 30, 40, 50µg/ml. The above dilutions are scanned in UV spectrophotometer for first order derivative in 220-240nm at N=5. Linearity and range for the first order derivative,the standard curve was obtained in the concentration range of 10-50μg/ml, the Slope, intercept and regression coefficient of standard curve was <0.999 for first order derivative and for area under curve shown table no 1.

Table no. 1: Linearity Data table and range of Vortioxetine Hydrochloride

Sr. No.	Concentration of Vortioxetine HCL	Absorbance at 220-240nm
1	10 µg/ml	0.009
2	20 µg/ml	0.015
3	30 µg/ml	0.021
4	40 µg/ml	0.027
5	50 µg/ml	0.032

d) Assay of tablet formulation:

The commercialized brands tablet strip (Brintellix) of Vortioxetine Hydrochloride was brought in for commercial formulation analysis. Determine the tablet's total weight. Then, take 10 tablet weights individually. It was necessary to crush the tablets. Prepare the 100µg/ml stock solution after calculating the weight to be taken. Consider the absorbance at 230nm. A mean assay value of 100.2% was obtained with a standard deviation of 0.5773.

RESULT:

Method Validation:

The above method was validated for various parameters such as Accuracy, Linearity, Precision, according to ICH guideline. Summary of validation parameters is given in table 2.

a) Linearity and Range:

The linearity was determined by using working standard solutions between 10-50µg/ml at 230nm and N=5. For the First order derivative results were recorded. Calibration curve for first order absorbance v/s concentration were plotted on excel sheet and linear regression was performed. The correlation coefficient, regression Equation was calculated. Details are shown in following graph and figures 1-3.

The Calibration curve of Vortioxetine Hydrochloride

Figure 1: Instrumental response of First derivative spectrum for 10µg/ml concentration.

Figure 2: Instrumental response of First derivative spectrum for 30µg/ml concentration.

Figure 3: Instrumental response of First derivative spectrum for 50µg/ml concentration.

b) Accuracy (Recovery Test):

Recovery experiments were used to assess the method's accuracy. The recovery experiments were carried out by introducing known amounts into the tablet. The recovery was carried out at three levels: 80, 100, and 120 percent of the standard concentration of Vortioxetine Hydrochloride. The recovery samples were prepared using the previously described procedure. For each level of recovery, three samples were prepared. The solutions were examined, and the percentage recoveries were determined using a formula.

Observed amount of compound in sample

% Recovery = ------------------------------------------ × 100

Amount of all compound present in sample

c) Precision:

Three independent assays of Vortioxetine Hydrochloride test sample were used to assess method precision. The method's intermediate precision was assessed using four different analyst and system in the same laboratory.

DISCUSSION:

The UV visible spectroscopic method for the Vortioxetine Hydrochloride by First order derivative was found to be simple, accurate, economical and reproducible. The drug concentrations were found to be linear in the range of 10-50µg/ml and the correlation coefficient value of 0.9988 indicates that developed method was linear. For Precision the percent relative standard deviation (%RSD) was found to be 0.3423 for the first order derivative respectively thus the method is observed as precise. The accuracy of the method was assessed by recovery studies at three different levels i.e. 80%, 100%, 120%. The values of standard deviation were satisfactory and the recovery studies were close to 100%. The %RSD value is ≤ 2 indicates the accuracy of the method.The result of the analysis for pharmaceutical formulation by the developed method was consistent with the label claim, highly reproducible and reliable. The validation parameters are summarized in Table 2. The method can be used for routine Novel spectrometric analysis of Vortioxetine Hydrochloride in pharmaceutical preparation.

Table no. 2: Summary of validation parameters.

Parameters	Results
Wavelength Range	230-240 nm
Measurement wavelength	230nm
Linearity range	10-50µg/ml
Slope	0.00058
Intercept	0
Correlation coefficient (R²)	0.9988
Accuracy(Mean% Recovery)	100.03
Precession(%RSD)	0.3423

CONCLUSION:

From the experimental studies it can be concluded that first order derivative method of Vortioxetine hydrochloride in pharmaceutical preparations. For specific medications, the recommended procedures were found to be precise and accurate. This procedure, on the other hand, is more repeatable. The results and statistical characteristics show that the suggested UV Spectrophotometric approach is straight forward, quick, precise, and accurate. The simplicity and speed of the Spectrophotometric approach are its most noticeable aspects. The results of the validation parameters showed that these analytical processes are suitable for their intended purpose and meet the ICH Q2/B standards.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGMENTS:

The authors are thankful for Apotex Research Pvt. Ltd. Bengaluru for their gift sample of pure drug for the studies.

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Received on 14.05.2022 Modified on 07.09.2022

Research J. Pharm. and Tech 2023; 16(7):3363-3366.

DOI: 10.52711/0974-360X.2023.00556

Table no. 2: Summary of validation parameters.

Parameters

Results

Wavelength Range

230-240 nm

Measurement wavelength

230nm

10-50µg/ml

0.00058

0

0.9988

Accuracy(Mean% Recovery)

100.03

Precession(%RSD)

0.3423