6. / ENCLOSURE-I
BRIEF RESUME OF THE INTENDED WORK:
6.1 .1 GENERAL DISCUSSION :
Mitiglinide[1,2] is a novel antidiabetic agent for the treatment of type-2 diabetes mellitus. Its chemical structure is similar to that of sulphonylureas. Mitiglinide exerts a hypoglycaemic effect with rapid onset and short duration of action, by transiently increasing insulin secretion. Mitiglinide is thought to stimulate insulin secretion by closing the ATP-sensitive K(+) (K(ATP)) channels in pancreatic beta-cells. Mitiglinide may also activate ryanodine receptors.
Structural Formula:

Nomenclature : 4-(1,3,3a,4,5,6,7,7a-octahydroisoindol-2-yl)-4-oxo-2-
(phenylmethyl)butanoic acid.
Molecular formula : C19H25NO3.
Molecular weight : 315.4067g / mol.
Characteristics : white or off-white crystalline powder.
Solubility : Easily soluble in Glacial acetic acid, Soluble in methanol,
slightly soluble in water.
Category : Hypoglycemic Agents.
Functional groups : Carboxyl group ,Carbonyl group.
6.2. NEED FOR THE STUDY:
Analytical methods are essential to characterize drug substances and drug products composition during all stages of pharmaceutical development. Development of methods to achieve the final goal of ensuring the quality of drug substances and drug products must be implemented in conjunction with an understanding of the chemical behavior and physicochemical properties of the drug substance.For routine analytical purpose it is always necessary to establish methods capable of analyzing huge number of samples in a short time period with high accuracy and precision.
There is constant development and change in the techniques and methods of analytical chemistry. These changes contribute to more economic analysis as they frequently lead to the elimination of time-consuming separation steps. The most demanding and perhaps the most rewarding one are the rational simple and accurate analytical methods for routine quantitative estimation of the drugs in bulk and commercial pharmaceutical dosage forms.Nowdays RP-HPLC is commonly used process for determination of the compound.
Mitiglinide is not official in any pharmacopoeia. Extensive literature survey reveals that not more methods were reported for determination of Mitiglinide in bulk drug formulations. UV-Visible spectrophotometric, HPLC[3], RP-HPLC[4],LC-ESI-MS[5-8], etc these methods were mostly developed in human plasma and urine. Due to this there is a need of suitable methods for routine analysis ofMitiglinidein bulk and its formulations. An attempt is being made to develop simple, precise and accurate analytical methods for estimation ofMitiglinide in pure sample and extend it for their determination in formulation.

6.3. REVIEW OF LITERATURE:

  1. Lushan Yu, et al[3].,Determination of Mitiglinide in rat plasma by high-performanceliquid chromatography with UV detection.
  2. Wang Jinzhao, et al[4].,Enantiospecific Analysis of Mitiglinide Calcium by RP-HPLC with precolumn derivatization.
  3. Shuang Cai, etal[5].,Quantitative determination of Mitiglinide in human plasma by liquidchromatography with electrospray ionization tandem mass spectrometry.
  4. Yan Liang, et al[6].,Sensitive, and Rapid LC–ESI-MS method for quantification of Mitiglinide in human urine.
  5. Jin Hua Wen,et al[7].,SPE and LC-ESI-MS for Quantitative analysis of Mitiglinide in human plasma in a bioequivalence Study.
  6. Liang J,et al[8].,High-performance liquid chromatography-electrospray ionization mass spectrometry determination of Mitiglinide in human plasma and its pharmacokinetics.
  7. Yan Zhang,et al[9].,Liquid chromatography/electrospray ionization tandem mass spectrometry for the quantification of Mitiglinide in human plasma: validation and its application to pharmacokinetic studies.
  8. Shu-Hhua Xiao,et al[10].,Determination of Mitiglinide in human plasma by liquidchromatography with electrospray ionization tandem massspectrometry.
6.4.OBJECTIVES OF THE STUDY:
Based on the literature, there are few analytical methods have been established for the quantitative estimation of Mitiglinide in human urine and plasma. Hence, there is necessity for development of new analytical methods for quantitative estimation of Mitiglinide in bulk drug and pharmaceutical dosage forms.
The main objective of the present work is:
  • Development of uv /vis spectrophotometricmethods for the estimation ofMitiglinidein bulk and dosage forms.
  • Development ofRP-HPLC, HPTLC method.
  • Validate the developed methods in accordance to ICH guidelines.
  • Analyze the marketed formulation for their reliability and accuracy.

7. / ENCLOSURE-II
7.1 MATERIALS AND METHODS:
Materials:
All the chemicals and reagents for the development of new analytical methods to estimateMitiglinidewill be of analytical grade.All qualitative and quantitative analysis of Mitiglinidewill be performed on Double beam UV-Visible Spectrophotometer (Shimadzu-1800), other Chromatographic instruments like HPLC (Shimadzu LC-20 AT) and HPTLC (Camag, Linomat-5)which are available in Department of Pharmaceutical Analysis in Bharathi College of Pharmacy.The pure sample of Mitiglinidefor the research work will be gifted by Ranbaxy Pharma, Ahmadabad. Marketed pharmaceutical dosage form or capsules will be purchased for local market.
Methods:
Analytical methods for the estimation ofMitiglinidewill be developed with high sensitivity, accuracy, precision and economy. These methods will be validated as per the ICH guidelines.[11,12,13] Following are the aforethought methods for the estimation of Mitiglinidein bulk and pharmaceutical dosage form:
Spectrophotometric methods based upon the solubility of Mitiglinidewill be developed, such as Difference Spectrophotometry, Derivative Spectrophotometry etc.
Chromatographic methods like HPLC, HPTLC will be planed dependingupon thechemical nature (polarity, functional groups) ofMitiglinide.
Other newmethods depending upon variousfunctional groups of Mitiglinidewill be planned.
7.2.SOURCE OF DATA:
  1. Library: BharathiCollege of Pharmacy.
  2. E-library: BharathiCollege of Pharmacy.
  3. Library, RGUHS Bangalore.
  4. Library IISE Bangalore.
  5. Internet.
7.3. METHOD OF COLLECTION OF DATA:
All the information noted here is compiled from the following journals and internet links:
Journals:
E-Journal of Chemistry
Oriental Journal of Chemistry
Journal of Pharmaceutical and Biomedical Analysis
Journal of Chromatography B
Indian Drugs
Chromatographia
Asian journal of pharmacodynamics and pharmacokinetics
Related links:






7.4.DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS?
NOT APPLICABLE
7.5. HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.4?
NOT APPLICABLE
8. / ENCLOSURE-III
REFERENCES :
  1. URL:
  2. URL:
  3. Lushan Yu, Zeng Su. Determination of Mitiglinide in rat plasma by high-performance liquid chromatography with uv detection. J Chromator B2006;834(1-2):204–207.
  4. Wang Jinzhao, Zeng Su, Gongyun Hu. Enantiospecific analysis of Mitiglinide calcium by rp-hplc with precolumn derivatization.JDrug anal2009;26(6):486-489.
  5. Shuang Cai, Taoguang Huo, Wanyu Feng, Lingyun Chen, Feng Qin, Famei Li. Quantitative determination of Mitiglinide in human plasma by ultra-liquidchromatography with electrospray ionization tandem mass spectrometry.J Chromatogr B2008;868(1-2):83-87.
  6. Yan Liang, Jie Sun, Lin Xie, Kang An, Yuan Xie, Wei-dong Chen, et al.Simple, Sensitive and rapid LC-ESI-MS method for quantification of Mitiglinide in human urine.J Chromatographia2007;66(3-4):165-170.
  7. Jin Hua Wen, Yu Qing Xiong. Spectroscopy and LC-ESI-MS for quantitative analysis of Mitiglinide in human plasma in a bioequivalence study. J Chromatographia2009;70(11-12):1715-1719.
  8. Jiabi Liang, Yuan Tian, Zunjian Zhang,Shudan Feng, Yanan Zhao, Guoguang Mao. High-performance liquid chromatography-electrospray ionization mass spectrometry determination of Mitiglinide in human plasma and its pharmacokinetics.J Mass Spectrom2007;42(2):171-177.
  9. Yan Zhang,Likun Ding, Yun Tian, Jing Yang, Lin Yang, Aidong Wen.Liquid chromatography/electrospray ionization tandem mass spectrometry for the quantification of Mitiglinide in human plasma: validation and its application to pharmacokinetic studies.J Biomed Chromat2008;22(8):873-878.
  1. Shu-Hhua Xiao, Guang-Lli Wei, Chang-Xiao Liu. Determination of Mitiglinide in human plasma by liquidchromatography with electrospray ionization tandem massspectrometry.Asian J Pharmacodyn Pharmacokinet2007;7(2):145-152.

11.ICH, Q2A Text on validation of analytical procedures, Oct, 1994.

  1. ICH, Q2B Validation of analytical methodology, Nov, 1996.
  2. ICH, Q2(r1) Validation of analytical procedures: text and methodology, 2005.