“METHOD DEVELOPMENT AND VALIDATION FOR QUANTITATIVE ESTIMATION OF DECITABINE OR OTHER CYTOTOXIC DRUGS BY HPLC.”
SYNOPSIS FOR REGISTRATION
OF
M.PHARM DISSERTATION
Submitted to
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA
By
SHILPASHREE.H.B
I M.PHARM
Department Of Pharmaceutical Chemistry
DAYANANDA SAGAR COLLEGE OF PHARMACY
2010
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BANGALORE
ANNEXURE - II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / Name of the Candidateand Address /
SHILPASHREE.H.B
D/o Balakrishna.K , # 89
P.Hosahalli , Sri Rangapatna taluk, Mandya-571438
2. / Name of the Institution / Dayananda Sagar College of Pharmacy,
Kumaraswamy layout, Bangalore – 560 078.
3. / Course of Study and
Subject / M.pharm in
Pharmaceutical Chemistry.
4. / Date of Admission / 3rd July 2010
5. / Title of The topic :
“Method Development And Validation For Quantitative Estimation Of Decitabine or Other Cytotoxic Drugs By HPLC.”
6.0 / Brief resume of the intended work:
6.1 – Need for the study:
The concept of analytical chemistry lies in the simple, precise and accurate measurements. These determinations require highly sophisticated instruments and methods like mass spectrometry, gas chromatography, HPTLC, HPLC, etc. HPLC method is sensitive, accurate, precise and desirable for routine estimation of drugs in formulations. Thereby it is advantageous than volumetric methods. Many HPLC methods have been developed and validated for the quantitative determination of various marketed drugs.
Analytical method development and validation plays an important role in drug discovery and manufacture of pharmaceuticals. These methods are used to ensure the identity, purity, potency and performance of drug products majority of analytical development effort goes into validating a stability indicating method. So it is a quantitative analytical method based on the structure and chemical properties of each active ingredient of the drug formulation.
Most of the drugs can be analyzed by HPLC method because of several advantages like rapidity, specificity, accuracy, precision reproducibility, ease of automation and eliminates tedious extraction and isolation procedures.
Hence the need of the study is to carry out the method development and validation for quantitative estimation of Decitabine or other cytotoxic drugs by HPLC as per ICH guidelines.
7.0 / 6.2 – Review of the literature:
1. Katan Patel , Sylvie M et al, have carried out simultaneous determination of decitabine and vorinostat (suberoylanalidehydroxamic acid, SAHA) by liquid chromatography tandem mass spectroscopy for clinical studies.
2. Zhongfa Liu1,4, Shujun Liu1,4, Zhiliang Xie 1,4, et al, investigated the characterization of in vitro and in vivo hypomethylating effects of decitabine in acute myeloid leukemia by a rapid , specific and sensitive LC-MS/MS method.
3. Christman JK et al, have studied 5-azacytidine and decitabine (5-aza-2- deoxy cytidine ) as inhibitors of DNA methylation ; They have done the mechanistic studies and their implications for cancer therapy.
4. Bryan T Hennessy , Guillermo Garcia- manero Hagop M Kantarjian , Francis J Giles carried out DNA methylation in haematological malignancies and discuss the role of Decitabine.
5. Isarita MARTINS , Jeferson O et al, have carried out the simultaneous determination of cyclophosphamide and Ifosfamide in plasma using SPE-HPLC-UV method.
6. M. Nagulu , V.Udaykiran, Y et al, have developed and validated new analytical method for the determination of methotrexate (cytotoxic) in human serum by rapid and sensitive HPLC method.
7. K. Ravikumar CH et al, have developed and validated RP-HPLC method for estimation of Capecitabine (cytotoxic) in capsules.
8. J.P.Tassin,J. Dubois,G et al, have carried out simultaneous determination of cytotoxic (Adriamycin,Vincristine) and modulator of resistance(Verapamil,S 9788) drugs in human cells by HPLC and ultraviolet detection.
9. Yong-Xing Zhao, Jian-Quig Gao,Hai-Ling Qiao,Hai-Liang Chen,Wen-Quan Liang have carried out development and validation of sensitive RP-HPLC method to determine intracellular accumulation of hydroxycamptothecin.
10. Ahmed F et al, have carried out development and validation of an HPLC method for the rapid and simultaneous determination of 6-mercaptopurine and four of its metabolites in plasma and red blood cells.
11. Yongbing Sun ,Jin Sun, Shiliang shi,Youjun Xu,Ying Chen,Yongjun Wang, Changqi Pan, Chunyu Zhang, Tianhong Zhang, Zhonggui He, have carried out HPLC/Tandem mass spectroscopy method for the simultaneous determination of cytarabine and its valyl prodrug valcytarabine in rat plasma.
6.3 – Objective of the Study:
In the proposed work, attempts shall be made to:
§ To develop new analytical method for the development and validation of decitabine or other cytotoxic drugs preferably by HPLC.
§ Validate the proposed method in accordance with ICH guidelines for the intended analytical application.
Materials and Methods:
7.1- Source of Data:
Literature survey and preliminary data require for the proposed study was done in various journals and in text books available with college and various institutions:
· Journal of chromatography B
· Journal of pharmaceutical and biomedical analysis
· Latin American journal of pharmacy
· Stamford journal of pharmaceutical sciences
· IISc library, Bangalore.
· DSCP library, Bangalore
· RGUHS digital library (Helinet), Bangalore
Web sites:
· www.sciencedirect.com
· www.pubmed.com
· www.google.com
· www.ijp-online.com
8.0 / 7.2 - Method of collection of data:
Chemicals & other reagents will be collected from standard companies. The standard protocols and ICH and FDA guidelines will be followed for validation of analytical procedures developed with the help of various journals and guidelines.
7.3 – Method development:
Analytical experiments will be planned and executed at Strides Arcolab Ltd. Bangalore and laboratories of Dayananda sagar college of pharmacy,
Bangalore. The following instrument is proposed to be used for collection of data.
v High Performance Liquid Chromatograph.
7.4 - Does the study require any investigations or interventions to be conducted on
patients or other humans or animals? If so, Please describe briefly.
NO.
7.5 - Has ethical clearance been obtained from your Institution in case of 7.4?
-NOT APPLICABLE-
List of References:
1. Katan Patel , Sylvie M. Guichard and Duncan I.Jodrel. Simultaneous determination of decitabine and vorinostat (suberoylanalidehydroxamic acid, SAHA) by liquid chromatography tandem mass spectroscopy for clinical studies. Cancer research U.K. , pharmacology and drug development group , University of Edinburgh Research Centre. Journal of Chromatography B. 2008:863:19-25
2. Zhongfa Liu, Shujun Liu, Zhiliang Xie , William Blum ,Danilo Perrotti,Peter Paschka,Rabecca Klisovic,Jhon Byrd,Keneth K.Chan and Guido Marcucci, Characterization of in vitro and in vivo hypomethylating effects of decitabine in acute myeloid leukemia by a rapid , specific and sensitive LC-MS/MS method. The Ohio State University , Columbus: 2006
3. Christman JK . 5-azacytidine and decitabine (5-aza-2- deoxy cytidine ) as inhibitors of DNA methylation : Mechanistic studies and their implications for cancer therapy. University of Nebraska Medical Center , USA, jchristm@ummc.edu.
4. Bryan T Hennessy , Guillermo Garcia- manero Hagop M. Kantarjian , Francis J Giles . DNA methylation in haematological malignancies : The role of Decitabine., University of Texas MD Anderson Cancer Center:2003:12(12): 1985-93
5. Isarita Martins, Jeferson O. Souja, Ananda L.Sanson, Elisabeth P.Viera and Alexandre Giusti-Paiva .Simultaneous determination of cyclophosphamide and Ifosfamide in plasma using SPE-HPLC-UV method. Latin American Journal of Pharmacy:2009:28(1):41-46
6. M. Nagulu , V.Udaykiran, Y. Narsimha reddy , D. Ramakrishna . Developement and validation of rapid and sensitive HPLC method for the determination of methotrexate (cytotoxic) in human serum .Stamford Journal of Pharmaceutical Sciences.2009:2(1):8-13.
7. K. Ravikumar , CH. M.M. Prasada rao, CH. Baburao, K.B. Chandra sekhar,P. Gangi Reddy. RP-HPLC method development and validation for estimation of Capecitabine (cytotoxic) in capsules. International Journal of Chem Tech Research:2010:2(1)307-11.
8. J.P.Tassin,J. Dubois,G .Atassi,M.Hanocq. Simultaneous determination of cytotoxic (Adriamycin,Vincristine) and modulator of resistance(Verapamil,S 9788) drugs in human cells by HPLC and ultraviolet detection.Journal of Chromatography B:1997:691:449-56.
9. Yong-Xing Zhao,Jian-Quig Gao,Hai-Ling Qiao,Hai-Liang Chen,Wen-Quan Liang. Development and validation of sensitive RP-HPLC method to determine intracellular accumulation of hydroxycamptothecin. Journal of pharmaceutical and Biomedical Analysis:2006:41:1007-10.
10. Ahmed F.Hawwsa,Jeff.S. Millership,Paul.S. Collier,James C. Mcelnay. Development and validation of an HPLC method for the rapid and simultaneous determination of 6-mercaptopurine and four of its metabolites in plasma and red blood cells.Journal of Pharmaceutical and Biomedical Analysis:2009:49:401-09.
11. Yongbing Sun,Jin Sun,Shiliang shi,Youjun Xu,Ying Chen,Yongjun Wang, Changqi Pan, Chunyu Zhang, Tianhong Zhang, Zhonggui He. HPLC/Tandem mass spectroscopy method for the simultaneous determination of cytarabine and its valyl prodrug valcytarabine in rat plasma. Journal of Chromatography B:2008:870:121-25.
9.0 / Signature of the candidate /
(Shilpashree.H.B)
10.0 / Remarks of the Guide:
11.0 / Name and Designation of:
11.1 Guide:
11.2 Signature: / Mrs. Kalpana Divekar
Associate Professor
Dept of Pharmaceutical Chemistry
Dayananda Sagar College of Pharmacy,
Kumaraswamy layout, Bangalore – 78.
11.3 Co-Guide:
11.4 Signature / Mr. Swamy.K.N
Team Leader, ASD
Strides Arcolab Ltd.,Opp.IIMB,
Bilekahalli, Bannerghatta Road,
Bangalore.
11.5 Head of the Department:
11.6 Signature / Dr. V. Murugan
Professor and principal
Dept of Pharmaceutical Chemistry
Dayananda Sagar College of Pharmacy,
Kumaraswamy layout, Bangalore – 78.
12.0 / 12.1 Remarks of the Chairman and Principal
12.2 Signature
/ Dr. V. Murugan
Professor and principal
Dept of Pharmaceutical Chemistry
Dayananda Sagar College of Pharmacy,
Kumaraswamy layout, Bangalore – 78.