Aspirin Raw Material Standard Analytical Procedure Practical aspects resulting from the implementation of the quality management system in companies in various fields (e.g., information for management of measurement equipment, standard operating procedures or dealing with deviations) allow to obtain a high-quality product. A fundamental role in the proper approach to the requirements imposed on companies in the pharmaceutical industry by the market is their compliance with ISO standards relating to quality management.
Aspirin Raw Material Standard Analytical Procedure
REFRENCE: BRITISH PHARMACOPOEIA 2020
APPROVAL BLOCK
| Title | Designation | Signature/Date |
| Written By: | Quality Control Analyst | |
| Reviewed By: | Quality Control Manager | |
| Verified By: | Quality Assurance In-charge | |
| Approved By: | Technical Operation Director |
Distribution List
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DOCUMENT REVISION CONTROL
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TABLE OF CONTENTS
1.0 PURPOSE
2.0 SCOPE
3.0 RESPONSIBILITY
4.0 REFERENCE
5.0 MATERIAL AND EQIUPMENT
6.0 PROCEDURE
7.0 RISK ANALYSIS
1.0 PURPOSE:
To describes the procedure for testing of raw material Aspirin
2.0 SCOPE:
This document describes the basic principles, defines the responsibilities and lays down the procedure for the analytical testing of Aspirin.
3.0 RESPONSIBILITY:
QC Analyst is responsible for physical / chemical testing and preparing standard analytical procedure.
It is the responsibility of QC Manager to assist and ensure Testing Procedure as per SAP and to make certain that this SAP is followed in its entirety, reviewed regularly and revised as necessary.
4.0 REFERENCE:
British Pharmacopoeia 2020
5.0 MATERIAL AND EQIUPMENT:
- Analytical balance
- FTIR
- HPLC
- Hot Plate
- Vacuum Assembly
- Muffle Furnace
- Spatula
- Sulphuric Acid
- Distilled Water
- Glassware
- Sodium Hydroxide
- Hydrochloric acid
- Phosphoric Acid
- Acetonitrile
- Alcohol
- Ethanol
- Phenolphthalein
- Salicylic acid
6.0 PROCEDURE:
6.1 SAMPLING PLAN:
Take sample from each container and identify individually. Make representative sample and divide into two portions. 1st portion for remaining analysis and 2nd portion for keeping sample.
6.2 RETAIN SAMPLE:
Pack sufficient quantity of sample in polythene bag and seal in aluminium foil finally. Keep the sample at recommended storage conditions for at least 1 year after expiry/retest date.
6.3 RECORD KEEPING:
Analysis records including raw data generated during the application of this procedure will be kept at least one year after the expiry or one year after the last distribution whichever is longer.
6.4 DESCRIPTION:
6.4.1 SPECIFICATIONS:
White or almost white, crystalline powder or colourless crystals.
6.4.2 PROCEDURE:
- Place 5gm of sample on the watch glass, observe physically the colour of sample, nature of the substance and extraneous matter present.
- Observe for any lumps or non-homogeneity.
- For odour, examine the sample immediately after opening the bag.
- If any odour is noticeable, open container and re-examine after 15 minutes.
- If the odour is still discernible, the sample does not comply with the description odorless.
- Spread approximately 2.0 g of the sample over the cleaned and dried petri dish and examine visually against white background. Check the appearance of color, nature and any visible foreign particles.
6.5 SOLUBILITY:
6.5.1 SPECIFICATIONS:
- Freely soluble: Take 1.0 gm of the material in 100 ml of stopper flask and add 10 ml of ethanol shake vigorously for one minute and keep aside for 15 minutes. The material should completely dissolve.
- Soluble: Take 1.0 gm of each material in two separate 100 ml of stopper flask and add 30 ml of chloroform in one flask and 30 ml of ether in another flask shake vigorously for one minute and keep aside for 15 minutes. The material should completely dissolve.
- Sparingly soluble: Take 1.0 gm of the material in 250 ml of stopper flask and add 100 ml of absolute ether shake vigorously for one minute and keep aside for 15 minutes. The material should completely dissolve.
- Slightly soluble: Take 1.0 gm of the material in 1000 ml of volumetric flask and add 1000 ml of distilled water shake vigorously for one minute and keep aside for 15 minutes. If sample has not been completely dissolved repeat shaking for two minutes and keep aside for 15 minutes. The material should completely dissolve.
Slightly soluble in water, freely soluble in ethanol (96 per cent).
| Each gram of solute in mL of Solvent | Sparingly Soluble | From 30 To 100 | |
| Very Soluble | Less Than 1 | Slightly Soluble | From 100 To 1000 |
| Freely Soluble | From 1 To 10 | Very Slightly Soluble | From 1000 To 10000 |
| Soluble | From 10 To 30 | Practically Insoluble | More Than 10000 |
- Retransfer accurately 1 g or the quantity specified in the test requirement, of the sample into precleaned, dried, stoppered test tube or Nessler cylinder.
- Add an appropriate volume of the specified solvent. Determine the volume of the solvent. The solution should be clear and free from foreign particles.
6.6 IDENTIFICATION
6.6.1 SPECIFICATIONS:
Identification by HPLC & by FTIR
6.6.2 PROCEDURE:
6.6.2.1 By HPLC
The retention time of the major peak in the chromatogram of the test solution should corresponds to that in the chromatogram of the standard solution, as obtained by HPLC method.
6.6.2.2 By FTIR:
Infrared absorption spectrum of the sample should be concordant with that of the standard
6.7 LOSS ON DRYING
6.7.1 SPECIFICATION:
LOD = Not More Than 0.5%.
6.7.2 PROCEDURE
1.000 g by drying in vacuo.
6.8 SULPHATED ASH
6.8.1 SPECIFICATIONS:
NMT 0.1%. Determine on 1.0 g Use a platinum, Silica, quartz, crucible.
6.8.2 PROCEDURE:
Ignite a suitable crucible (Silica or quartz) at 600 ± 50 °C for 30 min, allow to cool in a desiccator over silica gel or other suitable desiccant and weigh. Place the prescribed amount of the substance to be examined in the crucible and weigh. Moisten the substance to be examined with a small amount of sulfuric acid R (usually 1 mL) and heat gently at as low a temperature as practicable until the sample is thoroughly charred. After cooling, moisten the residue with a small amount of sulfuric acid R (usually 1 mL), heat gently until white fumes are no longer evolved and ignite at 600 ± 50 °C until the residue is completely incinerated. Ensure that flames are not produced at any time during the procedure. Allow the crucible to cool in a desiccator over silica gel or other suitable desiccant, weigh it again and calculate the percentage of residue. Unless Otherwise specified, if the amount of residue so obtained exceeds the limit specified in the individual monograph, repeat the moistening with sulfuric Acid, Heating and igniting as before using a 30- minute ignition period, until two consecutive weighing of the residue do not differ by more than 0.5mg or until the percentage of residue complies with the limit in the individual Monograph.
Calculate the percentage of residue by following formula;
- % age Sulfated ash= Weight of Residue x 100 / Weight of Sample Taken
- Weight of empty Crucible =A
- Weight of Crucible with Sample =B
- Weight of Sample =C
- Weight of Crucible with Sample after ignition= D=
- Weight of Residue= D-A= E
- Residue on Ignition (% w/w) = E x 100 / C
6.9 RELATED SUBSTANCES
6.9.1 SPECIFICATIONS:
6.9.2 MOBILE PHASE: Prepare a filtered and degassed mixture of phosphoric acid, Acetonitrile and water (2:400:600). Make adjustments if necessary
6.9.3 TEST SOLUTION:
Dissolve 0.100 g of the substance to be examined in Acetonitrile for chromatography R and dilute to 10.0 mL with the same solvent.
6.9.4 REFERENCE SOLUTION A:
Dissolve 50.0 mg of salicylic acid R (impurity C) in the mobile phase and dilute to 50.0 mL with the mobile phase. Dilute 1.0 mL of the solution to 100.0 mL with the mobile phase.
6.9.5 REFERENCE SOLUTION B:
Dissolve 10 mg of salicylic acid R (impurity C) in the mobile phase and dilute to 10.0 mL with the mobile phase. To 1.0 mL of the solution add 0.2 mL of the test solution and dilute to 100.0 mL with the mobile phase.
6.9.6 REFERENCE SOLUTION C:
Dissolve with the aid of ultrasound the contents of a vial of acetylsalicylic acid for peak identification CRS (containing impurities A, B, D, E and F) in 1.0 mL of Acetonitrile.
6.9.7 CHROMATOGRAPHIC SYSTEM:
- Detection wavelength: 237nm
- Column: C18 (4.6 mm × 250mm, 5μm)
- Flow rate: 1.0 mL/min
- Column temperature: Ambient
- Injection Volume: 10 µL
PROCEDURE:
Separately inject equal volumes (about 10 μL)of the standard preparation and the assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks.
6.1.1 SYSTEM SUITABILITY:
6.1.1.1 RESOLUTION
Minimum 6.0 for Reference solution B.
6.1.2 ACCEPTANCE CRITARIA:
Impurities A, B, C, D, B, F: For each impurity, not more than 1.5 times the area of the principal peak in the Chromatogram obtained with reference solution (A) (0.15 %).
Unspecified impurities: For each impurity, not more than 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).
Total impurities: Not more than 2.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.25 per cent).
6.10 ASSAY
6.11 ACCEPTANCE CRITARIA: 99.5 per cent to 101.0 per cent (dried substance).
6.12 PROCEDURE:
In a flask with a ground-glass stopper, dissolve 1.000 g in 10 mL of ethanol (96 per cent) R. Add 50.0 mL of 0.5 M sodium hydroxide. Close the flask and allow to stand for 1 h. Using 0.2 mL of phenolphthalein solution R as indicator, titrate with 0.5 M hydrochloric acid. Carry out a blank titration. 1 mL of 0.5 M sodium hydroxide is equivalent to 45.04 mg of C9H8O4.
6.1.3 STORAGE:
Preserve in tight containers, protected from light. Store at room temperature.
7 RISK ANALYSES:
EVIDENCE OF RECORDS & REFERENCES
USP44, NF39 Certificate of Analysis Raw Material
FORMAL KPIs (Key Performance Indicators)
Storage Condition Contamination of sampling tools