INTRODUCTION:

Escitalopram is the pure S-enantiomer of the racemic bicyclic phthalene derivative, citalopram. Escitalopram is designated as S-(+)-1-{3-(dimethyl-amino)propyl}-1-)(p-fluorophenyl)-5-phthalancarbonitrile¹. Escitalopram was launched and marketed worldwide with success as oxalic acid salt. Escitalopram oxalate is an orally administered selective serotonin reuptake inhibitor anti depressant, developed for the treatment of depression and anxiety disorders. It is also reported that it will be used to treat panic and compulsive disorders. S-(+) enantiomer being the pharmacologically active compound than R-(-) enantiomer^2-⁶. Escitalopram exhibits linear pharmacokinetics and its half life in human is 27.0-32.0 hrs⁵.

Literature survey revealed that various methods have been reported for determination of escitalopram in human plasma and its applications in bioequivalence study⁷, flourimetry quantitation plasma⁸, validation of capillary electrophoresis for simultaneous determination of impurities⁹, chiral LC method for separation of enantiomers¹⁰,simultaneous determinations of escitalopram and clonazepam in combined dosage forms^11-13. Santhosh Gandhi et al¹¹ in their article an UV spectrophotometric determination of escitalopram oxalate in combined dosage form contemplated the derivative UV spectrophotometric method with water as solvent.

It’s thought to try with organic solvents for routine and precise analysis of escitalopram for laboratory purposes. However by using methanol as solvent one can expect less interference from the excipients which are mostly water soluble. Present study involves development of simple method for the estimation of escitalopram oxalate in tablet dosage form by UV spectrophotometric method.

The objective of the report was to suggest a simple, rapid, and accurate UV spectrophotometric method for the determination of escitalopram oxalate in bulk sample and solid dosage forms. From the solubility studies drug was found to be freely soluble in methanol. An absorption maximum was found to be 239nm when the spectrum was scanned for the drug dissolved in methanol.

MATERIALS AND METHOD:

A Systronics UV-Visible spectrophotometer 117 with 1 cm matched quartz cells were used for estimation. AR grade methanol was used as a solvent in the study obtained from E-Merck, India. Pharmaceutical grade of escitalopram oxalate drug sample obtained as gift from Sibra pharmaceuticals, Hyderabad, India. Commercially available formulations Lexapro was procured from U.S market while Nexito was obtained from Indian market.

Standard preparation:

About 100mg of escitalopram oxalate was accurately weighed and dissolved in methanol made up to 100ml with the same solvent to get a concentration of 1mg/ml and diluting 10ml of this solution to 100ml with the same solvent in order to get a working standard of solution containing 100µg/ml.

Method:

Suitable aliquots of the standard solution of escitalopram oxalate (5.0-25.0ml) were transferred to a series of calibrated 100ml standard volumetric flasks and the volume in each flask was adjusted to 100ml with methanol. These solutions were scanned over the range of 200-350nm against blank. Absorption maximum was found to be 239nm (Fig 1). The calibration curve was constructed for absorbance Vs concentrationn of escitalopram oxalate.

Fig .1 Absorption spectrum of escitalopram oxalate (5 µg/ml)

Wave Length (nm)

Estimation of escitalopram oxalate in tablets:

Twenty tablets of escitalopram oxalate were weighed and powdered in glass mortar. The quantity of powder equivalent to 10 mg of escitalopram oxalate was transferred in to 100ml volumetric flask, dissolved in about 50 ml methanol and flask was kept for ultrasonication for 20 min, then it was diluted up to the mark with methanol to obtain the concentration of 100 µg/ml. The solution was filtered through Whatmann 42 filter paper. The sample solution was diluted and analyzed as described above.

Method Validation:^14-16

Accuracy of the method was determined by the recovery studies in the tablet formulation of escitalopram oxalate. Recovery studies were carried by addition of known quantities of standard drug solution to pre analyzed sample at three different concentrations. The precision of the method was demonstrated by analyzing sample of escitalopram oxalate on the same day and on three different days over a period of week. The percent coefficient of variance (%CV) was calculated. The LOD and LOQ for escitalopram oxalate was calculated from the linearity data using relative standard deviation of the response and slope of the calibration curve.

RESULTS AND DISCUSSION:

The proposed method is simple, precise, accurate and do not suffer from any interference due to common excipients of tablets. Escitalopram oxalate exhibits its maximum absorption at 239nm and obeyed Beer’s law in the range of 5.0-25.0 μg/ml (Fig 2). The proposed method of determination of escitalopram oxalate showed molar absorptivity of 0.1742x10⁵L/mol.cm. Linear regression of absorbance Vs concentration yielded equation Y=0.0414x+0.0029 with a correlation coefficient of 0.9999. The amount of escitalopram oxalate present in the sample solution was calculated from Beer’s plot. The results were shown in Table 1. Method was validated in terms of accuracy and precision. The accuracy of the method was ascertained by performing recovery studies in the commercially available formulations. The percentage recovery value 99.75%-100.82% indicates that there is no interference from the excipients presents in the formulation. The results were given in Table 2. The precision of method was checked in terms of interday and intraday where method was repeated on three different days and also repeated on three different time periods in the same day. The results showed 0.516 and 0.861 as % RSD for intra and inter day studies respectively. Summary of optical and regression parameters were shown in Table 3.

TABLE – 2: Recovery of escitalopram oxalate using the proposed UV method

S. No	Amount of drug added (μg)	*Mean(±SD)amount found(μg)**	Mean(±SD)* % of recovery
1	0.8	0.798 ± 0.04	99.75 ± 0.43
2	1.0	0.997 ± 0.05	99.71± 0.46
3	1.2	1.210 ± 0.05	100.8 ± 0.52

^*Average of three determinations

TABLE – 3: Optical characteristics of escitalopram oxalate

S. No	Parameter	Observation
1	λ _max	239nm
2	Beer’s Law Limit (µg/ml)	5—25 µg/ml
3	Molar Extinction Coefficient (Lmol^-1cm^-1)	0.1742×10⁵
4	Limit of detection (µg/ml)	0.35
5	Limit of quantitation (µg/ml)	1.16
6	Correlation Coefficient	0.9999
7	Regression Equation: Slope Intercept	0.0414 0.0029
8	%RSD	0.65

Fig. 2. Linearity of escitalopram oxalate (UV)

Hence the developed method was found to be sensitive, accurate, precise and reproducible and thus can be used for the routine quality control analysis of escitalopram oxalate in bulk drug and formulations which also works out to be economical.

ACKNOWLEDGEMENTS:

We are grateful to Sibra Pharmaceuticals, Hyderabad (India), for providing a gift sample of drug for research work. One of us (A.S) is thankful to Management, Hindu College of Pharmacy, Guntur for providing laboratory facilities and constant encouragement.

REFERENCES:

1. The Merck Index, An Encyclopedia of Chemicals, Drugs and Biologicals, Merck and Co., Inc., White house station 2001.

2. Lesola U.M, Wade A.G, Leinonen E.V et al. Journal of Clinical Psychiatry. 1998; 59: 528.

3. Sanchez C, Bogeso K.P, Ebert B et al. Psychopharmacology. 2004; 174(2): 163.

4. Mork A, Kreilgaard M and C. Sanchez. Neuropharmacology. 2003; 45: 167.

5. Hyttel J, Boefesoe K.P, Perregaard J and Sanchez C. Journal of Neural Transmission. 1992; 88: 157.

6. Bjerkenstedt L, Flyckt L, Overo K.F and Lingjaerde O. European Journal of Clinical Pharmacology. 1985; 28 (5): 553.

7. Sonu Sundd Singh, Hiten Shah, Sapna Gupta, Manish Jain and Kuldeep Sharma. Journal of chromatography B. 2004; 811: 205.

8. Serebruany, Victor, Malinin, Alex, Dragan et al. Clinical Chemistry andLaboratory Medicine. 2007; 45(4): 513.

9. Bunleu Sung thong, Pavel Jac and Gerhard K.E. Scriba. J.Pharm. Biomed. Anal. 2007; 46(5): 959.

10. Nagarjuna. A, Raghavacharyulu. K.S.V, Bindu.H.K and Mukkanti. K. Indian Drugs. 2004; 43(9): 746.

11. Santosh Vilashchand Gandhi, Milesh Dnyandev Dhavale, YJ.Vijay and Shweta Sabnis. Journal of AOAC International. 2008; 91(1):33.

12. Mahadeo M.V, Sunil D.R and .Mahesh K.J. Eurasian Journal of Analytical Chemistry. 2007; 2(2): 101.

13. Nilesh Dhavale, Santosh Gandhi, Shweta Sabnis and Kailash Bothara. Journal of Chromatographia. 2008; 67: 487.

14. International conference on Harmonization, guide lines on validation procedure, definition terminology federal register.1995; 60:11260.

15. The United States Pharmacopeia (USP 24) Asian edition, published by the United States Pharmacoepial Convention, Inc USA 2000.

16. P.D. Sethi. HPLC quantitative analysis of pharmaceutical formulations. Fifth edition, CBS publications, India. 2001; 160.

Received on 03.05.2010 Modified on 02.07.2010

Asian J. Research Chem. 3(4): Oct. - Dec. 2010; Page 935-937

Formulation	Label claim (mg)	*Amount found (mg)**	Mean ((±SD) %Drug found*	% RSD
Lexapro	10mg	9.8 mg±0.212	98.0±1.48	1.51
Nexito	10mg	9.85mg±0.256	98.5±1.06	1.08