REVIEWED PPT OF SULPHONAMIDES

Information about REVIEWED PPT OF SULPHONAMIDES

Published on October 3, 2012

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Analysis of sulphonamides: Analysis of sulphonamides 10/3/2012 1 Presented by… J.N.V. Indira Devi M.Pharmacy 1 st year Pharmaeutical analysis Yalamarty pharmacy college PowerPoint Presentation: INTRODUCTION CLASSIFICATION MECHANISM OF ACTION METHOD OF ANALYSIS RECENT METHOD OF ANALYSIS CONCLUSION REFERENCES 10/3/2012 2 Introduction: Introduction Sulphonamide is derived from Prontosil ,a prodrug that is metabolised invivo by Azoreductase . Anti bacterial drugs used in the treatment of infections caused by bacteria (gram positive and gram negative bacteria). Available in the form of tablets, suspensions,parenterals , opthalmic solutions,ointments . 10/3/2012 3 Classification: Classification 10/3/2012 4 Sulphadiazine Sulphathiazole sulphamethoxazole sulphadoxine Structures of sulphonamides: Structures of sulphonamides 10/3/2012 5 Mechanism of action : Mechanism of action 10/3/2012 6 Sulfonamides (such as sulfamethoxazole) and diaminopyrimidines (such as trimethoprim ) inhibit different enzymes in the biosynthesis of tetrahydrofolate in the bacteria. Due to the inhibited production of tetrahydrofolate, the bacteria is unable to synthesize the thymidine, and is therefore also unable to produce new DNA or RNA. This eventually leads to the death of the bacteria. Analytical methods for sulfadrugs: Analytical methods for sulfadrugs Titrimetric method : a)Diazotization titration b) B romination c) Nonaqueous titration d) Argentometric titration U.V- spectrophotometry Colorimetry Chromatography Fluorimetry 10/3/2012 7 Sulphadiazine: Sulphadiazine 10/3/2012 8 Chemical formula:C 12 H 14 N 4 O 2 S IUPAC name:4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzene-1-sulfonamide Indication :For the treatment bacterial infections causing bronchitis, prostatitis and urinary tract infections. Do not take calcium, aluminium , magnesium or iron supplements within 2 hours of taking this medication. DIAZOTISATION: DIAZOTISATION When aromatic primary amines with nuclear –NH2 groups can be determined quantitatively by standard sodium nitrite solution required to convert them into diazonium salts. 10/3/2012 9 PowerPoint Presentation: Standardisation of 0.1N NaNO 2 : Each ml of 0.1M NaNO2 ≡ 0.01732g of C 6 H 7 NO 3 S 10/3/2012 10 DETERMINATION OF SULFADIAZINE REAGENTS: Sodium Nitrite (0.1M) Starch Indicator: 750mg KI +5ml water 100ml hot water + 2g of ZnCl 2 i n 10ml water + 5g of starch in30ml water, cooled ∆ 2min PowerPoint Presentation: ASSAY PROCEDURE: 10/3/2012 11 CALCULATION: ( V2-V1) ×M× E.W %Sulfadiazine = W× 10 V 1 = vol of the NaNO 2 used in blank titration V 2 = vol of the NaNO 2 used for sample M = Molarity of NaNO 2 E.W=Equivalent weight of the sample W =Weight of the sample BROMINATION: BROMINATION PRINCIPLE: The sulfonamides reacts with bromine which will substitute on the benzene moiety The reaction is H 2 NC 6 H 4 SO 2 NHR+2HBr H 2 NC 6 H 2 Br 2 SO 2 NHR+2HBr Br 2 +2KI 2KBr+I 2 I 2 +2Na 2 S 2 O 3 2NaI+Na 2 S 4 O 6 METHODS FOR BROMINATION: Excess Method of Wojhan Direct Titration Method of Wojhan Excess Method of Conway Direct Method of Conway 10/3/2012 12 PowerPoint Presentation: EXCESS METHOD OF WOJHAN: PROCEDURE: DIRECT TITRATION METHOD OF WOJHAN: Similar method except the indicator is changed (methyl red) and then titrated with 0.1N KBrO 3 and end point gives the disappearence of red colour 10/3/2012 13 PowerPoint Presentation: EXCESS METHOD OF CONWAY: PROCEDURE: DIRECT METHOD OF CONWAY: The sample prepartion is as above.Five drops of alcoholic methyl red are added.The solution is titrated with Bromate -Bromide to the disappearence of red colour . 10/3/2012 14 SULPHATHIaZOLE: SULPHATHIaZOLE 10/3/2012 15 Chemical Formula C 9 H 9 N 3 O 2 S 2 IUPAC Name 4-amino-N-(1,3-thiazol-2-yl)benzene-1-sulfonamide Indication: effective against a wide range of gram positive and gram negative pathogenic microorganisms. Although no longer used in humans, it is used in cattle. NON-AQUEOUS TITRATIONS: NON-AQUEOUS TITRATIONS For determination of weak acids and weak bases TYPES Acidimetry in non –aqueous titration Alkalimetry in non –aqueous titration The sulfonamides contain weak acid group, so we are using alkalimetry in NAT. In these titration: Titrants used : Sodium methoxide,potassium methoxide,Lithium methoxide. Solvents: a . Strong base solvents: n-butyl amine , Morpholine b. Weak base solvents: DMF,Anhydrous pyridine Indicators: Azoviolet,O-nitroaniline,Thymolphthalein,p-hydroxy azobenzene 10/3/2012 16 DETERMINATION OF SULPHATHIAZOLE: DETERMINATION OF SULPHATHIAZOLE REAGENTS: 0.1N alkali methoxide.Ex:CH 3 ONa: 2. Thymol blue indicator 10/3/2012 17 PowerPoint Presentation: STANDARDISATION : Sodium methoxide Vs Benzoic acid 10/3/2012 18 PowerPoint Presentation: ASSAY PROCEDURE 10/3/2012 19 CALCULATION: % Sulphathiazole = (V 1 -V 2 )×M× E.W W× 10 V 1 = Volume of the titrant used for the blank solution V 2 = Volume of the titrant used for the sample solution M= Molarity of titrant E.W= Equivalent weight of the sample W= Weight taken . ARGENTOMETRIC TITRATION: ARGENTOMETRIC TITRATION PRINCIPLE: Argentometric titration is otherwise known as Precipitation titration Argentometry involves the use of the standard solution of silver nitrate as the titrant for estimation of the halides( chlorides,bromides & iodides) 10/3/2012 20 PowerPoint Presentation: PROCEDURE: 10/3/2012 21 Whole mixture is allowed to stand in dark The ppt is collected on double fold filter paper Wash ppt with water Filterate is acidifed with HNO3 Excess AgNO3 is titrated with 0.1N Ammonium thiocyanate Using ferric alum indicator SULPHAMETHAZINE: SULPHAMETHAZINE 10/3/2012 22 Chemical Formula: C 12 H 14 N 4 O 2 S IUPAC Name: 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzene-1-sulfonamide Indication:For the treatment bacterial infections causing bronchitis, prostatitis and urinary tract infections. UV-SPECTROPHOTOMETRY: UV-SPECTROPHOTOMETRY Estimation of sulfamethazine : 10/3/2012 23 COLORIMETRY: COLORIMETRY Analysis of sulfa drugs is done by converting primary amino group of sulfonamides into a diazonium salt by diazotisation and later coupling with suitable chromogenic agent to form Azo dye 10/3/2012 24 Chromogenic reagents Para dimethyl amino benzaldehyde method Brotton-marshall reagent α -1,2-naphthaquinone-4-sulphonate sodium( folin’s reagent) Thiobarbituric acid method α - napthol method Diazotisation followed by addition of alkali PDAB (Para dimethyl amino benzaldehyde )method: PDAB (Para dimethyl amino benzaldehyde )method Drug solution is treated with solution of PDAB under acidic conditions results in formation of AZOMETHINE,a yellow colour chromogen . Measured at λ max :440nm. It is an example of schiff”s base formation 25 R 1 =H R 2 =C 6 H 5 -N(CH 3 ) 2 R 3 =C 6 H 5 SO 2 NH-R YELLOW SCHIFF’S BASE PDAB SULPHONAMIDE 10/3/2012 DIAZOTISATION FOLLOWED BY COUPLING WITH BM REAGENT: DIAZOTISATION FOLLOWED BY COUPLING WITH BM REAGENT NH 2 SO 2 DIAZONIUM SALT N 2 ⁺ cl⁻ NHCHCHNH 2 NHCH2CH2NH2 SO 2 NH 2 BM REAGENT ( N-1-NAPHTHYL-ETHYLENE DIAMINE DIHYDRO CHLORIDE) N=N 10/3/2012 26 PINK AZODYE PowerPoint Presentation: 10/3/2012 27 Unknown should be compared with standard of same concentration as the system obeys Beer’s law. Absorbance measured at 545nm. Sulfonamide(mg)= Absorbane of sample × standard(mg) absorbance of standard CHROMATOGRAPHIC METHOD: CHROMATOGRAPHIC METHOD 10/3/2012 28 FLUORIMETRY : FLUORIMETRY 10/3/2012 29 RECENT METHOD OF ANALYSIS: RECENT METHOD OF ANALYSIS 10/3/2012 30 Analysis of sulfonamides by capillary electrophoresis 1.Rodrigo Hoff 2 , 2.Tarso B. L. Kist 1,3 Article first published online: 13 FEB 2009 DOI: 10.1002/jssc.200800738 Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA , Weinheim From:Journal of Separation Science Several methods for the determination of SFAs by CE have been published in recent years, and the present review considers applications in quality control of pharmaceutical dosage forms, food analysis, determinations in serum, and other biological fluids as well as in electrophoresis experiments which examine the behavior of this class of compounds for theoretical studies of the technique. This review covers studies ranging from the pioneering works on sulfonamide analyses using classical electrophoresis to the more recent CE methods coupled to tandem mass spectrometers. The sections are divided following the EC modes like CZE, MEKC, and hyphenated methods (CE-MS, CE-MS/MS). Parameters such as recoveries, LOD and LOQ, among others, are examined, covering works published until August 2008. PowerPoint Presentation: 10/3/2012 31 Liquid chromatographic determination of multiple sulfonamide residues in bovine milk: collaborative study. by M D Smedley Journal of AOAC International (1994) Volume: 77, Issue: 5, Pages: 1112-1122 PubMed : 7950413 Available from www.ncbi.nlm.nih.gov A collaborative study involving 8 laboratories was conducted on the determination of 8 sulfonamide residues in raw bovine milk using a liquid chromatographic (LC) method. The sulfonamides are extracted with chloroform-acetone, the organic phase is evaporated, the residues are dissolved in an aqueous potassium phosphate solution, and the fatty residues are removed by washing with hexane. The aqueous layer is collected, filtered, and injected onto an LC system, and the analyte is detected by ultraviolet (UV) absorption at 265 nm. : 10/3/2012 32 To quantitate all 8 sulfonamides isocratically , 2 chromatographic conditions are required: 12% methanol in the mobile phase for 5 sulfonamides, and 30% methanol in the mobile phase for 4 sulfonamides. Sulfamethazine (SMZ), the most widely used sulfonamide, is detected by both systems. Collaborators were instructed to analyze 3 replicates each of control milk and control milk fortified at 3 levels. They were also provided with 20 blind incurred samples (10 samples in duplicate) to analyze. For 10 ppb fortified milk, the average interlaboratory recovery for the 8 sulfonamides ranged from 56.2% for sulfaquinoxaline (SQX) to 82.7% for SMZ in the 12% methanol mobile phase (SMZ12). Also at this level, Sr ranged from 3.2 for SQX to 8.9 for SMZ12, and SR ranged from 6.9 for sulfadimethoxine to 17.2 for SMZ in the 30% methanol system (SMZ30). At 10 ppb, RSDr and RSDR ranged from 5.7% for SQX to 10.8% for SMZ12, and 10.1% for sulfamerazine to 20.9% for SMZ30, respectively. These results demonstrate that the method is suitable for the determination of the 8 sulfonamide residues in milk at 10 ppb. However, the identification of positives by this procedure needs additional confirmation by procedures comparable to the specificity achievable by liquid or gas chromatography combined with mass spectrometry. Rapid determination of sulphonamides in milk using liquid chromatographic separation and fluorescamine derivatization : Rapid determination of sulphonamides in milk using liquid chromatographic separation and fluorescamine derivatization 10/3/2012 33 Journal of Chromatography A Volume 607, Issue 1 , 21 August 1992, Pages 31–35 Nobuyuki Takeda , Yumi Akiyama Food and Drug Division, Hyogo Prefectural Institute of Public Health, Arata-cho , Hyogo- ku , Kobe 652 Japan http://dx.doi.org/10.1016/0021-9673(92)87051-9 , How to Cite or Link Using DOI A simple and selective method is presented for the multiple residue determination of eight sulphonamides in consumers' milk. The drugs are sulphisomidine (ID), sulphadiazine (DZ), sulphamerazine , sulphadimidine , sulphamonomethoxine , sulphamethoxazole , sulphadimethoxine and sulphaquinoxaline (SQ) The milk sample was deproteinized with the same volume of 2 M hydrochloric acid and filtered. A 1-ml volume of the tiltrate was mixed with 1 ml each of 1.25 M sodium acetate solution and a buffer (pH 3.0) for derivatization with 0.6 ml of 0.02% fluorescamine solution in acetone. A high-performance liquid chromatographic analysis was carried out on a C 18 column with a mobile phase of acetonitrile-2% acetic acid (3:5) at 55°C using a fluorescence detector at an excitation wavelength of 405 nm and an emission wavelength of 495 nm. Average recoveries at fortification levels of 2, 5 and 10 ng /ml were 114%, 109% and 106%, respectively. Relative standard deviations were 1–4% at 10 ng /ml. The limit of determination was 10 ng /ml for ID, 5 ng /ml for DZ and SQ and 2.5 ng /ml for the other five sulphonamides . The method was applied to 25 milk samples and all appeared to be free from the drugs. Liquid chromatographic–tandem mass spectrometric determination of selected sulphonamides in milk : Liquid chromatographic–tandem mass spectrometric determination of selected sulphonamides in milk 10/3/2012 34 Journal of Chromatography A Volume 960, Issues 1–2 , 25 June 2002, Pages 121–133 Special Volume Dedicated to the Memory of Professor J.F.K. Huber (1 January 1925 - 15 August 2000) J.A. van Rhijn a , , J.J.P. Lasaroms a , , B.J.A. Berendsen a , U.A.Th . Brinkman b a State Institute for Quality Control of Agricultural Products (RIKILT), Bornsesteeg 45, PO Box 230, 6700 AE Wageningen , The Netherlands b Department of Analytical Chemistry and Applied Spectroscopy, Free University, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands http://dx.doi.org/10.1016/S0021-9673(02)00329-1 , How to Cite or Link Using DOI Ultrafiltration is the only sample pre-treatment technique which is required. Consequently, sample throughput is much higher than with conventional procedures, and analyte recoveries are high. As for quantification, both external standard and isotope dilution calibration yield satisfactory results. The method is fully validated for five sulphonamides with a maximum residue limit of 100 μg /kg, and which are included in the Dutch control programme on residues. Furthermore, results are presented on the applicability of the method to detect compounds at a much lower concentration level exemplified by a banned sulphonamide , dapsone , which has a provisional action limit of 5 μg /kg. The main conclusion is that the present, novel approach to the trace-level determination of veterinary drugs is simple and straightforward and has a wide-ranging application potential which is briefly exemplified by the analysis of selected benzimidazoles in milk by essentially the same procedure. CONCLUSION: CONCLUSION I here by conclude that there is a much necessity for the study of analytical methods of sulphonamides as they are widely used class of drugs as Anti bacterial agents…. 10/3/2012 35 REFERENCES: REFERENCES The Indian Pharmacopoeia1996 P. D. Sethi , “Quantitative Analysis of Drugs in Pharmaceutical Formulations”,. B. Morelli , J. Pharm. Biomed. Anal.,1989, 7 , 577. P. B. Issopoulos , Acta . Pharm. Hung.,1992, 6 , 3138. M. Knochen , J. Giglio and B.F. Reis, J. Pharm. Biomed. Anal., 2003, 33 , 191. K.A Connors :Text book of Pharmaceutical Analysis,Third edition,Page no:(62-63 Higuchi,Beckmman&Hassan :Pharmaceutical Analysis,second editiom,Page no:(137-157) V.N Rajasekharan,Text book of Pharmaceutical In Organic Chemistry,Page no (126-128) 10/3/2012 36 PowerPoint Presentation: 10/3/2012 37 PowerPoint Presentation: 10/3/2012 38

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