“DEVELOPMENT AND VALIDATION OF

NEW ANALYTICAL METHODSFOR QUANTITATION OF RASAGILINE”

DISSERTATION PROTOCOL

SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.

BY

VAISHNANI BHAVINKUMAR KANTILAL

M.PHARM, PART-I

DEPARTMENT OF QUALITY ASSURANCE

NARGUNDCOLLEGE OF PHARMACY

BANGALORE-85

(2009-2011)

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / NAME OF THE CANDIDATE
AND ADDRESS (IN BLOCK LETTERS) / VAISHNANI BHAVINKUMAR KANTILAL
NARGUND COLLEGE OF PHARMACY,
DATTATREYANAGAR, II MAIN,
100 FEET RING ROAD,
BSK III STAGE,
BANGALORE-85,
KARNATAKA.
2. /

NAME OF THE INSTITUTION

/

NARGUND COLLEGE OF PHARMACY,

DATTATREYANAGAR, II MAIN,
100 FEET RING ROAD,
BSK III STAGE,
BANGALORE-85,
KARNATAKA.
3. /

COURSE OF STUDY AND SUBJECT

/ MASTER OF PHARMACY IN
QUALITY ASSURANCE
4. / DATE OF ADMISSION OF COURSE / 1ST JUNE2009.
5. /

TITLE OF TOPIC

/ “DEVELOPMENT AND VALIDATION OF NEW ANALYTICAL METHODS FOR QUANTITATION OF RASAGILINE”
6.
6.1 / BRIEF RESUME OF THE INTENDED WORK:
NEED FOR THE STUDY:
Parkinson’s disease is common neurodegenerative disorder typified by loss of dopaminergic neurons from the basal ganglia, and by a characteristic clinical syndrome with cardinal physical signs of resting tremor, bradykinesia and rigidity1. There are many anti-parkinsonism drugs are available in market as monotherapy or as adjunct therapy.
Rasagiline is an effective drug in market used for treatment of parkinsonism. It is a highly potent, selective and irreversible second generation mono amino oxidase inhibitor2. It is selective for MAO type B over type A by a factor of fourteen3, which is being developed for treatment of parkinson’s disease. MAO-B inhibitors cause an increase in extracellular levels of dopamine in the striatum. Rasagiline also possesses neuroprotective properties that are independent of its MAO inhibitory activity4, 5.
Hence, investigation of new analytical method is in need for the estimation of Rasagiline in bulk and in pharmaceutical dosage form.
6.2
6.3
7.
7.1
7.2
7.3
7.4
8. / REVIEW OF LITERATURE:
Chemically, Rasagiline is (R)-N-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-amine.
Molecular formula is C12H13N and molecular weight is 171.238 g/mol.
Predicted water solubility is 2.49e-02 mg/ml6.
Chemical structure of Rasagiline6

  • Marcos Fernandez et al. worked on development and validation of RP-LC method for quantification of Rasagiline Mesylate in biodegradable PLGA microspheres. Chromatographic separation was carried out using RP-18 column using mobile phase consisting of acetonitrile:water (5:95 v/v) adjusted at pH 3.1. Flow rate was 1.0 ml/minand UV detection was carried at 290 nm. Acyclovir was used as the internal standard7.
  • Taijun Hang et al. studies aimed at developing and validating rapid and sensitive LC–MS/MS method for determination of Rasagiline in human plasma and urine. It was carried out on LC-TSQ quantum mass spectrometer using positive ion electro spray ionisation (ESI) and selected reaction monitoring (SRM)8.
  • Jinfei Maet al.determined quantitatively Rasagiline in human plasma by LC–MS/MS method. The analytical method utilized liquid-liquid extraction of plasma with n-hexane:dichloromethane: isopropanol (20:10:1 v/v/v). Separation of analyte and the internal standard (IS) pseudoephedrine was performed on a C18 column (150 x 4.6 mm, 5 micron) with a mobile phase acetonitrile : 5mM ammonium acetate: acetic acid (40:60:0.05 v/v/v) at a flow rate of 0.5 ml/min9.
OBJECTIVES OF THE STUDY:
Literature survey reveals that, there is no spectrophotometric method available for the estimation of Rasagiline in bulk and various pharmaceutical dosage forms.
The objectives of the present work are,
  1. To develop UV-Visible spectrophotometric method for estimation of Rasagiline.
  2. To develop analytical method for quantitation of Rasagiline by HPLC.
  3. Validation of all developed analytical methods as per ICH guidelines.
MATERIALS AND METHODS
Materials:
Rasagiline, Rasagiline tablets, distilled water, hexane, ethylacetate, dichloromethane, methanol, acetonitrile, ethanol, chloroform, glacial acetic acid, acetone, propanol, phosphate buffer, ortho-phosphoric acid, hydrochloric acid, sodium hydroxide, potassium bromide, derivatising agents, etc.
Source of data:
Data will be obtained from Pubmed, Science direct, Medline, and other internet facilities, literature search and related articles from library of Nargund College of Pharmacy, Digital Library of RGUHS, Bangalore.etc.
Journals and articles:
  • Journal of Chromatography B
  • Journal of Pharmaceutical and Biomedical Analysis
  • Journal of Medicinal Chemistry
  • American Journal of Health System Pharmacy
Textbooks
  • A.H. Beckett, J.B. Stenlake, Practical pharmaceutical chemistry, 4th ed., Delhi: CBS publishers and distributors; 1997.
  • P.D. Sethi, Quantitative analysis of drugs in pharmaceutical formulation 3rd ed., Delhi: CBS publisher and distributors.
  • Takeru Higuchi, Einar Brochmann, Hanffen Hanssen, Hamffen Hanssen, Pharmaceutical Analysis, Delhi: CBS Publishers and distributors; 2005.
Internet Browsing
  • helinet.jccc.in
Method of Collection of Data (Including Sampling Procedure, If Any)
  1. Procurement of the drug and marketed formulations.
  2. Solubility determination of Rasagiline in different solvents and buffers.
  3. Determination of wavelength of maximum absorbance and intensity of absorption in different solvents and buffers for various analytical studies.
  1. Develop and validate analytical method for Rasagiline by UV-Visible spectrophotometer using standard absorptivity value, standard calibration curve, single point and double point standardisation.
  2. Develop and validate HPLC method to estimate Rasagiline in bulk and pharmaceuticalformulations.
Does the study require any investigation or intervention to be conducted on patients or other humans or animals? If so, please mention briefly.
NOT APPLICABLE
Has ethical clearance been obtained from your institution in case of 7.3?
NOT APPLICABLE
LIST OF ReferenceS:
  1. YoudimMB, Maruyama W, Naomi M. Long-term outcome of early versus delayed rasagiline treatment in early parkinson's disease. Drugs Today 2005;41(6):369.
  2. Binda C, Hubalek F, Li M. Binding of Rasagiline related inhibitors to human monoamine oxidases: a kinetic and crystallographic analysis. J Med Chem 2005; 48 (26): 8148–54.
  3. Oldfield V, Keating GM, Perry CM. Rasagiline: a review of its use in the management of Parkinson's disease. Drugs 2007; 67(12):1725.
  4. Chen JJ, Ly AV. Rasagiline: a second-generation monoamine oxidase type-B inhibitor for the treatment of Parkinson's disease. Am J Health Syst Pharm 2006; 63(10):915.
  5. Fernandez M, Barcia E, Negro S. Development and validation of RPLC method for the quantification of Rasagiline Mesylate in biodegradable PLGA microspheres. J Pharm Biomed Anal 2009; 49: 1185–91.
  6. Song M, Wang L, Zhao H, Hang T, Wen A, Yang L, Jia L. Rapid and sensitive LC–tandem mass spectrometry: Assay development, validation and application to a human pharmacokinetic study.J Chromatogr B 2008; 875: 515–21.
9. Ma J, Chen X, Duan X, Deng P, Wang H, Zhong D. Validated LC–MS/MS method for quantitative determination of Rasagiline in human plasma and its application to a pharmacokineticstudy. J Chromatogr B 2008; 873: 203-08.
9. / Signature of the candidate / (VAISHNANI BHAVINKUMAR KANTILAL)
10. / Remarks of the Guide / RECOMMENDED FOR THE DISSERTATION WORK.
11. / Name and Designation of
(in block letters)
11.1Guide
11.2 Signature / MRS. RITU VIVEK KIMBAHUNE
ASSISTANT PROFESSOR
DEPARTMENT OF QUALITY ASSURANCE
NARGUNDCOLLEGE OF PHARMACY
MRS. RITU VIVEK KIMBAHUNE
11.3 Head of the department
11.4 Signature / DR. J. N. NARENDRA SHARATHCHANDRA
Professor,HEAD OF THE DEPARTMENT
DEPARTMENT OF QUALITY ASSURANCE
NARGUNDCOLLEGE OF PHARMACY
DR. J.N. NARENDRA SHARATHCHANDRA
12. / 12.1 Remarks of Principal
12.2 Signature / FORWARDED AND RECOMMENDED FOR FAVOURABLE CONSIDERATION.
PROF. M.S. HARISH