INTRODUCTION:

Cyamemazine (Tercian), also known as cyamepromazine, is a typical antipsychotic drug of the phenothiazine class. It is used for the treatment of schizophrenia and especially, for psychosis-associated anxiety, due to its unique anxiolytic efficacy^1,2. Cyamemazine differs from other phenothiazine neuroleptics in that aside from the usual profile of dopamine, α1-adrenergic, H1, and mACh receptor antagonism³, it additionally produces potent blockade of several serotonin receptors, including 5-HT2A, 5-HT2C, and 5-HT7.^4,5,6

These actions have been implicated in cyamemazine's anxiolytic effects (5-HT2C) and lack of extrapyramidal side effects (5-HT2A),^5,6 and despite being classified as a typical antipsychotic, it actually behaves like an atypical antipsychotic⁷. The chemical structure of cyamemazine tartrate is shown in Figure 1.

From the thorough literature survey few analytical methods have been reported for the determination of cyamemazine tartrate in pure drug and pharmaceutical dosage form using UV Spectroscopy⁸LC-MS/MS⁹, GC-MS tandem mass spectrometry¹⁰ and HPTLC method¹¹. Hence an attempt was made to develop and validate simple, rapid and reliable analytical method to quantify cyamemazine tartrate in bulk and its formulation. The developed method was validated in accordance with ICH Q2 (R1) guidelines¹².

The aim of the present research was broadly focused on the estimation of cyamemazine tartrate in bulk and its formulation by using UV –Spectroscopic method.

Fig. 1: Chemical Structure of Cyamemazine tartrate

MATERIALS AND METHODS:

Chemicals and reagents:

An analytically pure sample of cyamemazine tartrate (CYMT) was procured as gift sample from MSN laboratories (Hyderabad, India). Analytical reagent grade ethanol was purchased from SD Fine Chem. Pvt. Ltd and distilled water was used as diluent for further preparations of the drug.

Instruments used:

For the current study UV/VIS double beam spectrophotometer, Shimadzu 1800 incorporated with UV probe software was used for the sample data analysis and was scanned by 1 cm matched quartz cells.

Method development:

Selection of solvent:

The solvent was selected by based on the solubility of CYMT in various solvents like distilled water, methanol, ethanol and 50% ethanol. Ethanol was chosen as the solvent for CYMT depending on absorption maximum at its analytical wavelength.

Preparation of stock solutions:

API of CYMT was 10mg weighed and transferred into a 10 ml volumetric flask and dissolved in ethanol. Final concentration was made from the 1000μg/ml (stock solution). From the stock solution respected aliquots were prepared by distilled water and scanned between 200-400nm.

Calibration curve for cyamemazine tartrate:

From the standard stock solution cyamemazine respected aliquots are pipette out into 10ml volumetric flask and dilutions are made with distilled water to obtain concentration range from 2-12μg/ml and the solutions are scanned in the spectrum mode from 400 to 200 nm wavelength range. Normal absorption spectrum was obtained.

Analysis of Marketed formulation (Sample Preparation):

Drug equivalent to 10 mg of CYMT marketed formulation was weighed and transferred into 10 ml volumetric flask. The drug was dissolved in ethanol and to enhance the solubility, sonicated for 5mins. Finally the dilutions are made from the distilled water up to the mark. The prepared solutions are scanned in the range of 200-400nm. The results are shown in table 1 and fig 2 and 3.

Validation of developed method:

Linearity and Range:

Cyamemazine shows good linearity in the range of 2-12μg/ml. Standard calibration curve was plotted by taking concentration (μg/ml) on x-axis and absorbance values on y-axis. Calibration curve of this method was shown in fig 3. The results were tabulated in table 1.

Accuracy:

Accuracy is determined as the closeness of the true value of analyte concentration. To determine the accuracy of the proposed methods the recovery studies were carried out at different levels (80%, 100% and 120%). The procedure was repeated for three times. The mean percent recovery was calculated and the data was shown in table 2.

Precision:

It is an analytical procedure expressed as repeatability of set of results under the prescribed conditions. The precision studies were carried for both repeatability and intermediate precision (interday) and %RSD was calculated. Intraday studies were carried for all the samples and absorbance (n=6) was recorded. Inter-day studies were carried for repeated days and absorbance (n=6) was recorded. The %RSD was found to be less than 2.

Limit of Detection and Quantification (LOD and LOQ):

The LOD and LOQ were calculated from the slope of regression equation obtained from calibration curve and standard deviation was taken from precision studies. The LOD and LOQ was found to be 0.121 μg/ml and 0.367μg/ml respectively.

RESULTS AND DISCUSSION:

Method validation was done for the accordance with ICH guidelines Q₂(R₁). In this method CYMT shows the linearity in the concentration range of 2-12µg/ml with regression value of 0.999.Regression value must be not more than 0.999. The mean % recovery was found to be, 99.45% and %RSD was found to be less than 2% for precision studies. All the validation parameters are present in within the limit. So the developed method was simple, precise, economic and accurate spectrophotometric method for the effective quantitative determination of CYMT as an active pharmaceutical ingredient as well as in pharmaceutical preparations without the interferences of other constituent in the formulations. Overall summary of validation parameters were tabulated in Table 3.

Fig. 2: Overlay of zero order UV Spectra of Cyamemazine tartrate

Fig. 3: Calibration curve of Cyamemazine tartrate

Table 1: linearity results for cyamemazine tartrate

S. No	Concentration (µg/ml)	Absorbance ± Standard deviation
1	2	0.150 ± 0.001
2	4	0.254 ±0.0017
3	6	0.353± 0.001
4	8	0.448± 0.004
5	10	0.544± 0.001
6	12	0.645±0.002

Table 2: Accuracy results for Cyamemazine tartrate

Level of recovery	Spiked drug concentratio (µg/ml)	Amount found (µg/ml)	% Recovery
80%	8	8.00	101.32
100%	10	10.01	99.45
150%	12	12.03	97.60

Table 3: The total Summary of Optical characteristics and Other Parameters

S. No	Parameters	Results
1	λ- max / wavelength range (nm)	270 nm
2	Beer’s law limit (μg/ml)	2-12
3	Correlation coefficient (R²)	0.9998
4	Regression equation	Y=0.0491x+0.029
5	Slope (m)	0.0491
7	Intercept	0.029
8	Intraday precision (% RSD)	0.330
9	Interday precision (% RSD)	0.778
10	Accuracy (% mean recovery)	99.45
11	Limit of detection (μg /ml)	0.121
12	Limit of quantification (μg / ml)	0.367
13	Assay	100.91

CONCLUSION:

A simple UV spectrophotometric method was developed for the estimation of cyamemazine tartrate (CYMT) in bulk and its pharmaceutical dosage form using Ethanol as solvent. From the results of validation parameters, it is proved that the method is simple, precise, reliable and accurate. Hence this method effective for the routine analysis of cyamemazine tartrate in bulk and pharmaceutical dosage form.

AKNOWLEDGEMENT:

I thank MSN laboratories, Hyderabad for providing a gift sample of cyamemazine tartrate. I would also like to thank Director, JNTUA-OTPRI for providing necessary facilities to carry out this research work.

REFERENCES:

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Received on 20.10.2018 Accepted on 04.12.2018

Asian J. Pharm. Tech. 2019; 9(1):08-10.

DOI: 10.5958/2231-5713.2019.00002.3