Spectrophotometric Determination of Atomoxetine Hydrochloride from Its Pharmaceutical Dosage Forms
Koradia SK*, Shah PT, Rana RR, Vaghani SS, Pandey S and Jivani NP
Smt. Rupaben B. Patel Mahila Pharmacy College, Atkot-360 040 Gujarat, INDIA
*Corresponding Author E-mail: shailesh_koradia@yahoo.com
ABSTRACT
A simple, economic and reproducible spectrophotometric method has been developed for the determination of HCl in bulk and in its pharmaceutical formulations. The spectrophotometric method was carried out at maximum absorbance of 270.0 nm for Atomoxetine HCl using double distilled water (DDW) as a solvent. The linearity over the concentration range of Atomoxetine HCl was found to be 20-180 μg/ml with correlation coefficient 0.9997. The detection limit and quantitation limit were found to be 4.04 μg/ml and 12.25 μg/ml, respectively. Results of analysis were validated statistically and by recovery studies. Commercial capsule formulations were successfully analyzed using the developed method.
KEYWORDS: Atomoxetine HCl, Spectrophotometry, Capsules, Method validation
INTRODUCTION:
Atomoxetine HCl, chemically is (-)-N-methyl-3-phenyl-3-(o-tolyloxy)-propylamine hydrochloride belongs to the class of antidepressant (fig. 1). Atomoxetine HCl is a selective norepinephrine reuptake inhibitor and is used to treat attention-deficit hyperactivity disorder (ADHD). Atomoxetine HCl is used to treat ADHD in children aged six years and older, adolescents and adults1. Literature survey revealed that HPLC2 and LC-MS-MS3 methods for the determination of Atomoxetine HCl have been reported. The drug is not official in any pharmacopoeias. In the present investigation, a sensitive, accurate and precise spectrophotometric method has been developed for the estimation of Atomoxetine HCl in capsule dosage forms.
MATERIAL AND METHODS:
Instrument: A double beam THERMO UV-Visible spectrophotometer, with spectral bandwidth of 2.0 nm, wavelength accuracy of + 0.5 nm and a pair of 1 cm matched quartz cells was used to measure absorbance of the resulting solution.
Materials: Pure drug sample of Atomoxetine HCl was obtained as a gift sample from Intas Pharmaceuticals Private Limited, Ahmedabad. Two brands of capsule formulations were procured from a local pharmacy and double distilled water
Preparation of standard Atomoxetine HCl solution:
Accurately weighed Atomoxetine HCl (100 mg) was transferred to a 100 ml volumetric flask, dissolved and made-up the volume to 100 ml with double distilled water (DDW). The final solution contained 1000 μg/ml of Atomoxetine HCl solution. This solution was used as working standard solution.
Preparation of calibration curve for Atomoxetine HCl:
Aliquots (0.2-1.8 ml) of standard Atomoxetine HCl solution (1000 µg/ml) were transferred to a series of 10 ml volumetric flasks, and were suitably diluted with DDW, to give final concentrations of 20-180 μg/ml. Aliquots were scanned in the range of 200 nm to 400 nm. The maximum absorbance of solution was found to be 270.0 nm. The absorbance of solution in each flask was measured at 270.0 nm against DDW. The calibration curve was constructed by plotting absorbance versus concentration.
Procedure for analysis of capsule formulations:
Twenty capsules were weighed and average weight was calculated. The capsules were mix properly to obtain fine powder. Capsule powder equivalent to 100 mg of Atomoxetine HCl was transferred to 100 ml volumetric flask and volume was made up to the mark with DDW and sonicated for 15 minutes. The solution was then filtered through a Whatmann filter paper (No. 41). The filtrate was appropriately diluted with DDW to obtain 50 μg/ml of Atomoxetine HCl.
Table 1: Summary of validation parameters
|
20 - 180 |
|
|
Limit of detection (µg/ml) |
4.04 |
|
Limit of quantification (µg/ml) |
12.25 |
|
Precision (% CV) · Repeatability · Intraday · Interday |
0.52-0.90 0.79-1.12 |
|
Accuracy (% recovery) |
99.84-100.49 |
|
Specificity |
Specific |
Table 2: Estimation of Atomoxetine HCl in pharmaceutical formulations
|
Label value(mg) |
% Label value found (Mean + SD)* |
Recovery ± % CV* |
|
|
Capsule-1 |
10 |
99.35 + 0.104 |
100.49 ± 0.85 |
|
Capsule-2 |
40 |
100.70 ± 0.630 |
99.84 ± 1.13 |
* Average of five determinations, SD is the standard deviation and CV is the coefficient of variation
Fig.1 Chemical structure of Atomoxetine HCl
Validation of method:4, 5
The proposed method was validated on the basis of parameters namely accuracy, precision, specificity, linearity, limit of detection and limit of quantitation (table 1). The accuracy of the method was ascertained by carry out recovery studies using standard addition method. The recovery study was performed to determine if there was any positive or negative interference from excipients present in the formulation. The precision of an analytical method is expressed as % CV (coefficient of variation) of a series of measurements. It was ascertained by replicate estimation of drug by the proposed method.
RESULTS AND DISCUSSION:
The results showed that the method has reasonable precision. Specificity was checked by spiking reference standard by placebo like calcium carbonate, talc and starch in different concentration. Limit of detection and limit of quantitation were studied based on standard deviation of the response and the slope of the line obtained by plotting absorbance versus concentration. Accuracy of the proposed method was carried out by adding known quantities of pure Atomoxetine HCl to its pre-analyzed formulations and the mixtures were analyzed by the proposed method. The results of recovery experiments are summarized in table 2.
CONCLUSION:
The proposed method for estimation of Atomoxetine HCl in capsule dosage forms was found to be accurate, rapid and simple. The values of coefficient of variance were satisfactorily low and percentage recovery was close to 100%, indicating reproducibility of the method. There was no interference of the excipients present in the capsules. Hence, it can be used for routine analysis of the Atomoxetine HCl in pharmaceutical formulations.
REFERENCES:
1. Sweetman SC. Eds., In; Martindale, The Complete Drug Reference, Pharmaceutical Press, London, UK, 34th edition. 2005.1585.
2. Sudhir SK, Vishal BC, Vinayak TV, Swarup SP. RP-LC Determination of Atomoxetine HCl from its Pharmaceutical Dosage Form. Cromatograhia 2007; 67:143-146.
3. Mulhen JM, Shugert RL, Ponsler GD. Simultaneous quantification of atomoxetine as well as its primary oxidative and O-glucuronide metabolites in human plasma and urine using liquid chromatography tandem mass spectrometry (LC/MS/MS). J Pharm Biomed Anal 2005; 38:720–733.
4. ICH Q2A; Guidelines on validation of analytical procedures; Definitions and terminology, Federal Register, 1995, 60, 11260.
5. ICH Q2B; Guidelines on validation of analytical procedures; Methadology, Federal Register, 1996, 60, 27464.
Received on 04.04.2009 Modified on 25.05.2009
Accepted on 28.06.2009 © AJRC All right reserved
Asian J. Research Chem. 2(3): July-Sept., 2009, page 258-259