“EVALUATION OF ANTIDIABETIC ACTIVITY OF HELICTERES



“ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR API INTERMEDIATES USING ADVANCED ANALYTICAL TECHNIQUE RAPID RESOLUTION LIQUID CHROMATOGRAPHY”

Synopsis for registration of M.pharm Dissertation

Submitted to

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BENGALURU.

KARNATAKA

[pic]

In partial fulfillment

of the requirement for the Degree of

Master of pharmacy In Pharmaceutical analysis

Under the Guidance of

AKKAMMA.H.G.

Asst. Professor

DEPARTMENT OF PHARMACEUTICAL ANALYSIS

BY

B.MADHURI PRIYANKA

I M. PHARM.

[pic]

DEPARTMENT OF PHARMACEUTICAL ANALYSIS

KARNATAKA COLLEGE OF PHARMACY, BENGALURU-64

2010-11

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BENGALURU.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

| | | |

|1. |Name of the candidate and address |B.MADHURI PRIYANKA. |

| | |Karnataka College of Pharmacy, |

| | |Thirumenahalli, |

| | |Bengaluru-560064, |

| | |Karnataka, India. |

| | | |

| | |PERMANENT ADDRESS: |

| | |B.MADHURI PRIYANKA. |

| | |D/O. B.Prasad Rao, |

| | |Opp. to Reliance Infocom, |

| | |Nallam Vari Street, Gunupudi, |

| | |Bhimavaram, |

| | |W.G (Dist.), |

| | |Andhra Pradesh-534201 |

| | | |

|2. |Name of the Institution |Karnataka College of Pharmacy, |

| | |Thirumenahalli, |

| | |Bengaluru-560064, |

| | |Karnataka, India. |

| |Course of study and subject | |

|3. | |M.Pharm-Pharmaceutical analysis. |

| |Date of the admission | |

|4. | |21-06-2010. |

| |Title of the topic |

|5. |“ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR API INTERMEDIATES USING ADVANCED ANALYTICAL TECHNIQUE RAPID RESOLUTION LIQUID |

| |CHROMATOGRAPHY” |

| | |

| | |

| |BRIEF RESUME OF THE INTENDED WORK: |

|6 | |

| |6.1 – NEED FOR THE STUDY: |

| |Active Pharmaceutical Ingredients (API) are active chemicals used in the manufacturing of drugs. Another term for Active Pharmaceutical |

| |Ingredient is Bulk Drug Substance. An API starting material is a raw material, intermediate or an API that is used in the production of an |

| |API and that is incorporated as a significant structural fragment into the structure of the API." And, it adds, as typical characteristics, |

| |"An API starting material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial |

| |agreement, or produced in-house. API starting materials normally have defined chemical properties and structure.(1) |

| |Generally many methods have been developed for the estimations of different drugs by using U.V, Mass Spectroscopy, G.C, and HPLC etc. But |

| |RRLC is more rapid and advanced method used for development and validation. |

| |On literature survey, it was found that RRLC is the more advanced method for analytical validation (4) which is the key for the process of |

| |validation. |

| |RRLC system was designed to provide highest analysis speed and resolution and at the same time keep system pressure at a minimum. Fastest, |

| |most efficient and most flexible LC system in the world. |

| |A recent trend in LC analysis today is to increase sample throughput to achieve higher laboratory productivity and efficiency. One way to |

| |speed up LC analysis is to replace long columns with short ones, to increase the flow rate and gradient steepness, to use LC systems that are|

| |capable of delivering gradient changes to the column with very low delay times. A parameter, which is not too often mentioned during these |

| |procedures, is the optimization of the column compartment temperature. A possible reason might be that LC systems, which are able to provide |

| |column device in front of the detector, are not commercially available. The elevated temperature up to 100oC help to increase speed of |

| |analysis and also help to improve resolution and peak shape.(2) |

| | |

| | |

| |6.2 VARIOUS EXAMPLES OF API: |

| |These include various categories of drugs. They are anti-inflammatory, anti- cancers, anti hypertensive, antifungals, leukotriene antagonists|

| |etc. |

| |Some examples of the above mentioned categories are: |

| |1.Telmisartan |

| |2.Esomeprazole |

| |3.zafrileukast |

| |4.Itraconazole |

| |5.Indomethacin |

| | |

| |DRUG PROFILE: |

| |TELMISARTAN: |

| |It is the new class of angiotensin receptor antagonist. It reduces effectively hypertension by suppressing the effects of angiotensin II at |

| |its receptor, there by blocking the renin-angiotensin system. Telmisartan shows comparable antihypertensive activity to other major |

| |antihypertensive classes, such as angiotensin converting enzyme (ACE) inhibitors, beta‐blockers and calcium antagonists because of its |

| |enhanced specificity, selectivity, and tolerability.9 Currently, Telmisartan is marketed alone or combined with Ramipril or |

| |Hydrochlorothiazide. Analytical methods that have have been reported for the determination of eprosartanin Pharmaceutical formulations by |

| |Spectrophotometric estimations.(3) |

| | |

| |STRUCTURE: |

| |[pic] |

| | |

| | |

| | |

| |IUPAC Name: |

| |4'[(1,4' Dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl)methyl][1,1'- biphenyl]-2-carboxylic acid. |

| |Molecular Formula : C33H30N4O2 |

| |Molecular Weight : 514.62 |

| |Category : Angiotensin receptor blocker |

| |Mechanism of action: |

| |It acts specifically as a competative antagonist at the AT1 receptor. Even angiotensin receptor blocker can be increase in bradykinin due to |

| |AT2. Unlike saralasin it lacks any intrinsic agonist property. Given orally it is well absorbed and undergoes first pass metabolism in |

| |liver.(3) |

| | |

| |ESOMEPRAZOLE: |

| |Esomeprazole is a compound that inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), |

| |the healing of erosive esophagitis, and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new |

| |class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonistic |

| |properties, but that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the|

| |gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, Esomeprazole has been |

| |characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to|

| |inhibition of both basal and stimulated acid secretion irrespective of the stimulus.(5) |

| |STRUCTURE: |

| |[pic] |

| |IUPAC Name: |

| |5-methoxy-2-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methylsulfinyl]-3H-benzoimidazole. |

| |Molecular Formula : C17H19N3O3S. |

| | |

| |Molecular Weight : 345.42 |

| |Category : proton pump inhibitor. |

| | |

| |Mechanism of Action: |

| |Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric |

| |parietal cell. By acting specifically on the proton pump, Esomeprazole blocks the final step in acid production, thus reducing gastric |

| |acidity.(5) |

| | |

| |ZAFIRLUKAST: |

| |Zafirlukast is an oral leukotriene receptor antagonist (LTRA) for the maintenance treatment of asthma, often used in conjunction with an |

| |inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. Another leukotriene receptor|

| |antagonist is montelukast (Singulair), taken once daily. Zileuton (Zyflo), also used in the treatment of asthma via its inhibition of |

| |5-lipoxygenase, is taken four times per day. Zafirlukast blocks the action of the cysteinyl leukotrienes on the CysLT1 receptors, thus |

| |reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages.(5) |

| |STRUCTURE: |

| |[pic] |

| | |

| |IUPAC Name: |

| |4-(5-cyclopentyloxy carbonylamino-1-methyl-indol-3-ylmethyl)-3-methoxy-N-o-tolylsulfonylbenzamide(ZAF). |

| |Molecular Formula : C31H33N3O6S. |

| |Molecular Weight : 575.7 g/mol. |

| |Category : Leukotriene antagonist. |

| | |

| | |

| | |

| |ZAFI: ZAF1is one of the Key Intermediate in Zafirlukast. |

| |STRUCTURE: |

| |[pic] |

| |Mechanism of Action: |

| |Zafirlukast is a selectively and competitive leukotriene-receptor antagonist (LTRA) of leukotriene D4 and E4 (LTD4 and LTE4), components of |

| |slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the |

| |pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory|

| |process, which contribute to the signs and symptoms of asthma.(5) |

| | |

| |6.2 REVIEW OF LITERATURE: |

| |JiFeng Yang et al., developed a simultaneous extraction and analysis method for analysis of four class of antibiotics sulfonamides (SAs), |

| |macrolides (MLs), fluoroquinolones (FQs) and tetracyclines (TCs) in sediment.(6) |

| |Tatsunari Yoshida et al., developed the potential of high-speed analyses by rapid resolution liquid chromatography (RRLC) and RRLC/MS.(7) |

| |Yuan-chun Ma et al., developed a simple, reliable and reproducible rapid resolution liquid chromatography (RRLC) method was for |

| |Shuang-Huang-Lian (SHL) a traditional Chinese formula which comprises of three medicinal herbs.(8) |

| |Geraldine Dowling et al., developed a rapid method to analyse carprofen (CPF), diclofenac (DCF), mefenamic acid (MFN), niflumic acid (NIFLU),|

| |naproxen (NAP), oxyphenylbutazone (OXYPHEN), phenylbutazone (PBZ) and suxibuzone (SUXI) residues in bovine milk. Aliquots were analysed by |

| |rapid resolution liquid chromatography tandem mass spectrometry (RRLC)-MS/MS).(9) |

| | |

| | |

| |Pablo de la lglesia et al., developed a method for the determination of dissolved Domoic acid DA and its isomers present in seawater based on|

| |a solid-phase extraction (SPE) disks followed by rapid resolution liquid chromatography coupled with tandem mass spectrometry.(10) |

| |E.M. Malone et al., developed a rapid method for the analysis of synthetic growth promoters in bovine muscle using liquid chromatography |

| |tandem mass spectrometry.(11) |

| |Lucie Nováková et al., carried out a review of current trends and advances in modern bio analytical methods by chromatography and sample |

| |preparation.(12) |

| | Mahesh Kumar Mone et al., reported An efficient stability indicating liquid chromatographic separation method was developed for |

| |pentoxifylline and its three degradation products (including two from base hydrolysis) using 1.8 μm, C18 reverse phase column and UHPLC.(13)|

| | |

| |6.3 OBJECTIVE OF THE STUDY: |

| |To contribute the development of analytical methods for a simple precise, rapid and cost effective estimation of the drugs in pharmaceutical |

| |Bulk forms. |

| |The fastest LC: Upto 20 times faster than HPLC with same or better performance. |

| |To develop a new sensitive and accurate RRLC method. |

| |The available methods for the intermediate were developed on conventional LC with longer retention times. |

| |The development was done on RRLC instrument, a recent advancement in chromatography technique. The method was developed on a short column |

| |with shorter Runtime. |

| |Validating the proposed newly developed methods in accordance with the analytical parameters mentioned in the IP,BP,USP, and ICH guidelines. |

| | |

| | |

| | |

| | |

| |MATERIALS AND METHODS |

| |7.1 Source of data: |

| |Literature survey was done at Karnataka College of Pharmacy using internet facilities and at library. |

| |Reference from library at RGUHS, Bengaluru. |

| |Indian institute of sciences, Bengaluru. |

| | |

| |7.2 Method Of Collection Of Data: |

| |In the present investigation of the validation of new analytical method for API’S in tablet dosage form is in need and RRLC with diode array |

| |detector and different solvent system and other chromatographic instruments. |

| |The entire instruments like Shimadzu -1700 UV- spectrophotometer, HPLC Agilent 1120, etc. are available. Development and validation of new |

| |analytical method of API’S shall be carried out at Department of Pharmaceutical Analysis, Karnataka College of Pharmacy. The lab is |

| |adequately equipped with necessary analytical setup to carry out desired work. |

| |For the selection of mobile phase to be used in RRLC different combination and ratio of solvent will be tried to obtain good retention time |

| |and chromatogram having optimum resolution. Various data collected for the analytical method development either by RRLC or HPLC will be |

| |treated statistically to find its compliance with ICH or Pharmacopoeial guidelines. Typical analytical parameters such as linearity, range, |

| |precission, specificity, accuracy, ruggedness and robustness used in assay validation will be determined. |

| | |

| |JOURNALS: |

| |Journal of pharmaceutical and bio medical analysis. |

| |Analytica chimica Acta. |

| |Journal of separation science. |

| |Journal of chromatography A. |

| | |

| | |

| |RELATED LINKS: |

| | |

| | |

| | |

| | |

| | |

| |library.ubc.ca/scieng/coden.html |

| | |

| | |

| | |

| | |

| |7.3 - Does The Study Require Any Investigation To Be Conducted On Patients Or Animals |

| |If So, Please Describe Briefly. |

| |No. |

| | |

| |7.4 – Has Ethical Clearance Been Obtained From Your Institution In Case Of 7.3? |

| |NOT APPLICABLE. |

| | |

| |REFERENCES: |

| |. |

| |Agilent . |

| |Tripathi K D. Essential of Medical Pharmacology 5th Ed. New Delhi:Jaypee Brothers Medical Publishers (P) Ltd; 2003.p. 489,631,222. |

| |ICH Harmonised Tripartite Guideline (Nov.2005) Validation of Analytical procedures: Text and Methodology Q2 (R1) International Conference on |

| |Harmonisation, Geneva, Switzerland. |

| |The Merk Index, an encyclopedia of chemicals, drugs and biological.Fourteenth ed.NJ; 2006. |

| |Ji-Feng Yang,Guang-Guo Ying ,Jian Liang Zhao,Ran Tao,Hao chang, Su and Feng Chen .simultaneous determination of four classes of antibiotics |

| |in sediments of the pearl rivers using RRLC-MS/MS Science of Total Environment 2010 Jul 15;408(16):3424-32. |

| |Tatsunari Yoshida, Ronald E Majors High speed analysis using Rapid Resolution Liquid Chromatography on 1.8 μm porous particles.J Sep sci |

| |2006;29(16):2421- 32. |

| |Yuan-Chun Ma, Xiao-Qiang Wang, FeiFei Hou, Jie Ma, Mai Luo, Alice Chen, Peter Jin, Shane Lu, Iris Xu RRLC Analysis amd studies on the |

| |stsbility of shuang-huang lian preparations. J Phm Bio Med Anl 2011 Jan 25;54(2):265-72. |

| |Geraldine Dowling Pasquale Galto Edward Malone Liam Regan. Rapid confirmatory analysis of N.S.A.I.D.S in bovine milk by RRLC tandem mass |

| |spectrometry. J chromatogr A 2009 Nov 13;1216(46):8117-31. |

| |Pablo de la Iglesia, Gemma Giménez, Jorge Diogène Determination of dissolved domoic acid in sea water with reverse phase extraction disks |

| |and RRLC tandem mass spectrometry with head coloumn trapping. J chromatogr A 2008 Dec;26(1-2):116-24. |

| |Malone E M, Elliott C T , Kennedy D G, Regan L development of rapid method for the analysis of synthetic growth prometers in bovine muscle|

| |using liquid chromatography tandem mass spectrometry. Anal chim Acta, 2009 Apr;1637(1-2):112-20. |

| |Lucie Nováková, Hana Vlčkova .A review of current trends in modern bio analytical methods: chromatography and sample preparation. Anal chim |

| |Acta, 2009 dec 10; 656(1-2):8-35. |

| |Mahesh Kumar Mone, Chandrasekhar K.B. Degradation of pentoxifylline isolation and characterization of novel and gem dihydroperoxide |

| |derivative as major oxidative degradation product. J pharm Biomed Anal 2010 Nov 2;53(3):335-42. |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| |9 |

| | |

| |Signature of the candidate |

| | |

| | |

| |[B.MADHURI PRIYANKA] |

| | |

| | |

| |10 |

| | |

| |Remarks of the Guide : The topic selected for dissertation is satisfactory. Adequate equipment and chemicals are available to carry out the |

| |project work. |

| | |

| | |

| |11 |

| | |

| |Name and Designation [BLOCK LETTERS] |

| | |

| | |

| | |

| |11.1 |

| |Guide |

| |AKKAMMA.H.G, |

| |ASST. PROFESSOR, |

| |DEPT OF PHARMACEUTICAL ANALYSIS, |

| |KARNATAKA COLLEGE OF PHARMACY, |

| |BENGALURU-64. |

| | |

| | |

| |11.2 |

| | |

| | |

| |Signature of Guide |

| | |

| | |

| | |

| |[AKKAMMA.H.G] |

| | |

| | |

| |11.3 |

| |Co-Guide |

| | |

| | |

| |--------- |

| | |

| | |

| |11.4 |

| |Signature of Co-Guide |

| | |

| |--------- |

| | |

| | |

| |11.5 |

| |Head of the Department |

| | |

| | |

|7 | |

| |Dr. C.SREEDHAR, |

| |PROFESSOR, |

| |DEPT. OF PHARMACEUTICAL ANALYSIS |

| |KARNATAKA COLLEGE OF PHARMACY, |

| |BENGALURU-64 |

| | |

| | |

| | |

| |11.6 |

| | |

| | |

| |Signature of HOD |

| | |

| | |

| | |

| |[DR.C.SREEDHAR] |

| | |

| | |

| |12 |

| | |

| |12.1 |

| | |

| |Remarks of the Principal : All the required facilities will be provided to carry out dissertation work under the supervision of guide. |

| | |

| | |

| |12.2 |

| | |

| | |

| | |

| | |

| | |

| | |

| |Principal |

| | |

| | |

| | |

| | |

| | |

| | |

| |DR.K. RAMESH. |

| |PRINCIPAL |

| |KARNATAKA COLLEGE OF PHARMACY |

| |#33/2, THIRUMENHALLI, |

| |HEGDE NAGAR MAIN ROAD, |

| |JAKKUR POST, |

| |YELAHANKA, HOBLI, BENGALURU. |

| | |

| | |

| | |

| |12.3 |

| | |

| | |

| |Signature of the Principal |

| | |

| | |

| | |

| | |

| | |

| |[Dr.K.RAMESH] |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

| | |

|8 | |

| |

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download