elemental impurities analysis mpharm pharmaceutical analysis ist sem mainly advanced pharmaceutical analysis subject

1. SEMINAR ON ELEMENTAL
IMPURITIES
KARNATAKA COLLAGE OF PHARMACY
PRESENTED BY PRAKASH GUPTA
M PHARM IST SEMESTER
DEPARTMENT OF PHARMACEUTICAL ANALYSIS
SUBMITTED TO DR. C SREEDHAR
HOD OF DEPARTMENT OF PHARMACEUTICAL ANALYSIS

2. TABLE OF CONTENTS
• ELEMENT CLASSIFICATION
• CONTROL OF ELEMENT IMPURITIES
• SOURCES OF ELEMENTAL IMPURITIES
• IDENTIFICATION OF POTENTIAL ELEMENTAL IMPURITIES
• ANALYTICAL PROCEDURES
• INSTRUMENTATION
• C , H , N , S ANALYSIS

7. DIFFERENT INSTRUMENTAL
ANALYTICAL METHODS FOR THE
IDENTIFICATION OF ELEMENTAL
IMPURITIES
• ATOMIC ABSORPTION SPECTROMETRY(AAS)
• X-RAY FLORESCENCE SPECTROMETRY(XRF)
• INDUCTIVELY COUPLED PLASMA ATOMIC EMISSION
SPECTROMETRY(ICP-AES)
• INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY(ICP-MS)

8. ATOMIC ABSORPTION SPECTROMETRY(AAS)
• THIS TECHNIQUE IS BASED ON THE PRINCIPLE THAT THE AMOUNT OF
LIGHT ABSORBED IS A MEASURE OF THE CONCENTRATION OF A
PARTICULAR ANALYTE AT A PARTICULAR WAVELENGTH.
• THE ANALYTES IN THE SOLUTIONS ARE CONVERTED INTO ATOMS IN
VAPOUR PHASE.
• THESE FREE ATOMS ARE THEN TRANSFORMED TO EXCITED STATE BY
ABSORPTION OF RADIANT ENERGY FROM AN EXTERNAL SOURCE.

9. INSTRUMENTATION
• NEBULIZER- PNEUMATIC NEBULIZER
• ATOMIZER- FLAME ATOMIZER, BURNERS
• SPECTROMETER
• DETECTOR- PHOTOMULTIPLIER DETECTOR

11. SAMPLE ANALYSIS
• PRETREATMENT OF SAMPLE- ANALYTE IS TO BE DISSOLVED IN A SUITABLE
SOLVENT IN ORDER TO UNDERGO NEBULIZATION.
• NEBULIZATION- IT IS THE BREAKDOWN OF ANALYTE SOLUTION INTO
SMALL DROPLETS.
• ATOMIZATION- CONVERSION OF ANALYTE IN AEROSOL INTO FREE STATE
FOR ANALYSIS.

12. SAMPLE ANALYSIS
• THE MAIN PROCEDURE USED FOR CARRYING OUT QUANTITATIVE
DETERMINATION IS THE SAMPLE SOLUTION IS FIRST ASPIRATED INTO THE
FLAME.

24. X-RAY FLORESCENCE SPECTROMETRY(XRF)
• XRF SPECTROSCOPY INVOLVES THE IRRADIATION OF THE
SAMPLE WITH HIGH ENERGY EXCITATION X-RAYS AND
MEASUREMENT OF ELEMENT SPECIFIC FLUORESCENCE X-
RAYS AT A PARTICULAR WAVELENGTH OR ENERGY FROM
THE SAMPLE. SAMPLE MAY BE IN SOLID, POWDER OR
LIQUID FORM.
• SINCE IT IS A NON-CONTACT ANALYSIS, PROBLEMS SUCH
AS MEMORY EFFECTS COMMONLY EXPERIENCED IN
SOLUTION ANALYSIS, ARE NOT ENCOUNTERED.

25. • AS IT IS A NON-DESTRUCTIVE TECHNIQUE, IT IS
POSSIBLE TO REUSE THE SAMPLE AFTER
MEASUREMENTS.
• BOTH FORMS, NAMELY, WAVELENGTH DISPERSIVE
XRF AND ENERGY DISPERSIVE XRF TECHNIQUES
HAVE BEEN SUCCESSFULLY APPLIED FOR THE
DETERMINATION OF ZN, FE, AND NI IN THE API’S.

26. C.H.N.S ANALYZER
• A CHN ANALYZER IS A SCIENTIFIC INSTRUMENT WHICH CAN DETERMINE THE
ELEMENTAL COMPOSITION OF A SAMPLE.
• THE ANALYZER USES A COMBUSTION PROCESS TO BREAK DOWN
SUBSTANCES INTO SIMPLE COMPOUNDS WHICH ARE THEN MEASURED.
• IN THIS TECHNIQUE THE SUBSTANCE UNDER STUDY IS COMBUSTED UNDER
OXYGEN STREAM IN A FURNACE AT HIGH TEMPERATURES.
• THE END PRODUCTS OF THE COMBUSTION WOULD BE MOSTLY THE OXIDES OF
THE CONCERNED ELEMENTS IN THE FORM OF GASES.

27. • THESE ARE THEN SEPARATED AND CARRIED TO THE DETECTOR USING INERT
GASES LIKE HELIUM OR ARGON.
• IT IS ONE OF THE FEW ANALYTICAL TECHNIQUES THAT GIVE A CLEAR QUANTITATIVE
MEASUREMENT OF THE CARBON, HYDROGEN, NITROGEN AND SULPHUR.
• CHN MICROANALYSIS IS A POWERFUL AND RELATIVELY STRAIGHT FORWARD
METHOD.
• WHICH IS USE FOR DETERMINING WHETHER OR NOT A SAMPLE IS PURE BY
PROVIDING A PRECISE AND ACCURATE ANALYSIS OF A SAMPLE'S PERCENTAGE
CARBON, HYDROGEN AND NITROGEN CONTENT.

28. • THE MAIN DRAWBACKS OF CHN ANALYSIS ARE THE
REQUIREMENTS FOR ACCURATE WEIGHING OF 1-2 MGS
OF SAMPLE (THAT IS CONSUMED IN THE ANALYSIS)
• AND ALSO THE FACT THAT SAMPLES ARE USUALLY RUN
AS AN AUTOMATED BATCH RATHER THAN ON AN
INDIVIDUAL SAMPLE BASIS.
• THE ANALYSIS OF RESULTS IS PERFORMED BY
DETERMINING THE RATIO OF ELEMENTS FROM WITHIN
THE SAMPLE, AND WORKING OUT A CHEMICAL FORMULA
THAT FITS WITH THOSE RESULTS.

29. • THE ACCEPTED DEVIATION OF ELEMENTAL ANALYSIS RESULTS
FROM THE CALCULATED IS 0.4%.
• THE METHOD FOR WORKING OUT THE RATIO OF ELEMENTS
FROM THE RESULTS IS SHOWN BELOW:
• 1. TAKE THE PERCENTAGE OF EACH ELEMENT FOUND AND
DIVIDE BY THE ELEMENT'S MASS. DO THIS FOR ALL THE
ELEMENTS FOR WHICH YOU HAVE RESULTS
• 2. FIND THE SMALLEST VALUE FROM STEP 1 AND DIVIDE
EVERY VALUE OBTAINED IN STEP 1 BY THIS SMALLEST VALUE

30. • 3. MULTIPLY THE RESULTS IN STEP 2 BY A FACTOR TO OBTAIN
REASONABLE VALUES FOR EITHER CARBON OR NITROGEN AND
THEN COMPARE TO WHAT WAS EXPECTED FROM A PURE
SAMPLE OF THE COMPOUND THAT WAS THOUGHT TO BE
SUBMITTED.
• THIS PROCESS IS TEDIOUS TO PERFORM BY HAND, AND
AUTOMATED TOOLS HAVE BEEN RELEASED TO SIMPLIFY WITH
THIS PROCESS.

31. • THE ORIGINAL ANALYSIS METHOD IS BASED ON THE COMPLETE AND INSTANTANEOUS
OXIDATION OF THE SAMPLE BY "FLASH COMBUSTION" WHICH CONVERTS ALL ORGANIC
AND INORGANIC SUBSTANCES INTO COMBUSTION PRODUCTS

32. SPECIFICATION
• MODEL: PERKIN ELMER, U.S.A 2400 SERIES II
• CHNS/O ELEMENTAL ANALYZER - PERKIN ELMER PE 2400
• ANALYZED ELEMENTS: CARBON, HYDROGEN, NITROGEN, SULFUR AND OXYGEN
• OPERATING MODE: CHN, CHNS AND OXYGEN
• ACCURACY: 0.3% ABS
• ANALYSIS TIME: 6 TO 8 MINUTES PER SAMPLE
• AUTOMATIC WEIGHT TRANSFER
• SAMPLE SIZE: 1 TO 200 MG
• MULTIPLE SAMPLE MODE IF REQUIRED: 60 SAMPLES
• SAMPLE COMBUSTION TEMPERATURE: AROUND 2000 º C.

33. HOW IT WORKS
• FROM THE COMBUSTION PRODUCT THE RESULTING COMBUSTION GASES PASS
THROUGH A REDUCTION FURNACE AND ARE SWEPT INTO THE CHROMATOGRAPHIC
COLUMN BY THE CARRIER GAS WHICH IS HELIUM.
• THE GASES ARE SEPARATED IN THE COLUMN AND DETECTED BY THE THERMAL
CONDUCTIVITY DETECTOR WHICH GIVES AN OUTPUT SIGNAL PROPORTIONAL TO
THE CONCENTRATION OF THE INDIVIDUAL COMPONENTS OF THE MIXTURE.
• THE RESULTS ARE COMPARABLE TO THOSE OBTAINED BY TRADITIONAL METHODS,
SUCH AS KJELDAHL AND DUMAS, BUT IT OFFERS FASTER ANALYSIS TIME WITH
GREATER REPRODUCIBILITY AND ACCURACY.

34. REFERENCES
GOOGLE.IN
• PULSE PUBLICATION
• WWW.SLIDESHARE.NET
•