Development and Validation of Spectrophotometric Method for Determination of Pramipexole  in Solid Dosage Forms.

 

Mayur G. Raval*, Preeti Tiwari and C.N. Patel

Shree Sarvajanik Pharmacy Collage, Near Arvind Baug , Mehsana-384001, Gujarat, India.

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

ABSTRACT:

The Objective Of the current study was to develop and validated UV spectrophotometric method for Pramipexole in solid dosage form. The method was validated by subjecting the drug to UV radiation. The drug was successfully quantified at 263 nm. The method was validated with respect to linearity, precision, accuracy, robustness. The response was linear over the range of 3-15 for Pramipexole. The recovery of the drugs from a mixture product was in the range of 99.00-101.46%. The utility of the procedure was verified by its application to marketed formulations. The specificity of the method was also checked with reference to placebo. The method was found to be specific also, hence other validation parameter were in  the limit also.

 

 

 

INTRODUCTION:

Accurate UV method development involves proper selection of solvent and wave length. The solutions of Pramipexole were run for calibration curve as well as for assay and validation. Method was found to be successful in accordance with the results ¹.

 

Pramipexole (INN, trade names Mirapex® and Sifrol®) is a medication indicated for treating Parkinson’s disease and restless legs syndrome (RLS). It is also sometimes used off-label as a treatment for cluster headache or to counteract the problems with low libido experienced by some users of SSRI antidepressant drugs. Pramipexole has shown robust effects on pilot studies in bipolar disorder. Pramipexole is classified as a non-ergoline dopamine agonist².

 

Pramipexole

 

MATERIALS AND METHODS:

Apparatus:

Spectroscopic evaluation was performed with Spectrophotometer  (Shimadzu Corporation, Japan).

 

Reagent and Material:

Pure Pramipexole sample from Zydus Cadila (Ahmedabad, Gujarat) with 97.4 % purity. Marketed products, label claim: 0.5 mg Pramipexole per tablet, Zydus Cadila LTD was taken.

Water (DM grade) was  prepared by in house technique.

 

Preparation of Standard Solutions:

Standard stock solution of Pramipexole (500µg/ml) was prepared in mobile phase. For the calibration plot of Pramipexole, varies dilution was prepared from the stock solution in range of 3-15  µg/ml. All the dilution was made with water.

 

Method Validation:

Linearity was established by triplicate observation of solution containing standard Pramipexole in the concentration range of 3-15  µg/ml. The system precision was established by making 6 replicate observation of standard solution containing 10µg/ml Pramipexole. The method precision was established by making 6 replicate observation of test solution containing 10µg/ml Pramipexole. Accuracy was determined by fortifying e mixture of test solution with 3 standard solution containing known concentration of Pramipexole (5, 10, 15 µg/ml) and percent recoveries of added drug were determined.      Robustness of the method was determined by deliberately varying certain parameter. The specificity was also checked by observing spectra of placebo.

 

RESULT AND DISCUSSION:

Fig.1 Overlay Spectra of Linearity Study:

 

Wavelength(nm)

 

Fig.2 Calibration Curve from Linearity Study:

 

Validation of Proposed Method:

The method was validated with respect to the following parameters given below;

 

Linearity:- Linearity calibration plot for above method was obtained in the calibration ranges of 3-15 µg/ml, and the correlation coefficient obtained were  greater than 0.999(Table  1).

 

LOD and LOQ – The LOD value for Pramipexole was 0.99µg/ml and the LOQ value for Pramipexole was 2.6 µg/ml.

 

Precision: - Data obtained from analysis of the sample on the same day (n=6) and on consecutive days(n=6) are given in the Table 4. The RSD values obtained were well below 2%. The RSD value indicates that the method is sufficiently precise. The intermediate precision established for the method showed that similar resolution was obtained when the experiment was conducted with 2 different days.

 

Accuracy:-  Percent recoveries were calculated from the differences between the absorbance obtained for the fortified and unfortified solutions. Good recoveries were obtained for each fortification level(Table 3) ,indicating that method is accurate.

 

Specificity: - The specificity of the  method was shown by no interference of placebo in observation.

Robustness:- The method remained robust even with small variation in wave length.(Table 5)

 

Applicability of Developed Method to Marketed Formulations (%Assay):

A solution containing sample of the Pramipexole was observed for the absorbance, and % assay is calculated.(Table.2)

 

Table 1. System suitability parameters for the determination of Pramipexole by proposed SPECTROPHOTOMETRIC method

Parameter	Pramipexole
Linearity Range	3-15  µg/ml
Regression Coefficient	0.999
Slop	0.023
LOD	0.99
LOQ	3

*Average of Six Replicate

 

Table 2.Assay result obtained for solid dosage form  by proposed SPECTROPHOTOMETRIC method.

Tablet	Pramipexle content mg/Tablet	Absorbance	% Assay ± SD
MIRAPREX	Pramipexole 0.5 mg	0.234	100.33± 0.0014

 

 

Table 3. Recovery studies for determination of Pramipexole by proposed SPECTROPHOTOMETRIC method.

Value	Set	mg added	Response	Percentage	% Recovered	Average
50	Set-1	25	0.117	49.78723404	99.57446809	99.00709
	Set-2	25	0.116	49.36170213	98.72340426
	Set-3	25	0.116	49.36170213	98.72340426
100	Set-1	50	0.238	101.2765957	101.2765957	101.4184
	Set-2	50	0.238	101.2765957	101.2765957
	Set-3	50	0.239	101.7021277	101.7021277
150	Set-1	75	0.358	152.3404255	101.5602837	101.4657
	Set-2	75	0.358	152.3404255	101.5602837
	Set-3	75	0.357	151.9148936	101.2765957
Standard for Calculation		0.235

*n = 3

 

Table 4 . Statistical evaluation of Precision  for determination of Pramipexole by proposed SPECTROPHOTOMETRIC method.

Parameter	Precision		Intermediate Precision
Value	System Precision	Method Precision		Wavelength(+)	Wavelength(+)
1	0.233	0.246	0.234	0.229	0.226
2	0.235	0.246	0.239	0.23	0.227
3	0.233	0.246	0.24	0.23	0.226
4	0.233	0.246	0.241	0.229	0.226
5	0.233	0.247	0.24	0.229	0.226
6	0.233	0.246	0.24	0.229	0.226
Average	0.23	0.246166667	0.239	0.229333333	0.226166667
Std. Dev.	0.00146385	0.000372678	0.002309401	0.000471405	0.000372678
%RSD	0.006364566	0.001513926	0.009662766	0.002055543	0.001647802

 

 

Table 5. Robustness  studies for determination of Pramipexole by proposed SPECTROPHOTOMETRIC method.

Compound	% RSD (n=5)
	Normal Condition	Changed Condition
Wavelength	Normal	(-5 nm)	(+5 nm)
Pramipexole	0.006	0.0016	0.002

 

 

CONCLUSION:

The SPECTROPHOTOMETRIC method for estimation of Pramipexole in its solid dosage form was established as per guidelines. The linearity of developed method for estimation was achieved in the range of 3-15 µg/ml (r²=0.999) for Pramipexole. From the validation results, we can conclude that our methods are simple, sensitive, rapid, linear, precise, rugged, accurate, and robust and hence they can be used for the routine analysis of Pramipexole in quality control department.

 

The work described in this paper has shown that the developed method is precise, accurate, linear. The method was found to be specific to the drugs, because the spectra  of placebo did not interfere with the drug. Application of this method to the determination of Pramipexole  in tablet dosage form shows that the excipients did not interfere with the analysis.. .

 

REFERENCES:-

1.       Kasture AV, Wadodkar SG, Mahadik KR, More HM. Introduction to Instrumental Techniques. 12^th edn, Pune: Nirali Prakasan;2005, vol 3 ,pp.1-10.

2.       Available online at URL  http\\www.Wikipedia.com /Pramipexole

 

 

Received on 06.06.2011        Modified on 19.06.2011

Accepted on 08.07.2011        © AJRC All right reserved