by ANALYTICAL METHOD VERIFICATION PROTOCOL FOR ASSAY OF NAPROXEN Ph. Eur.
| Superseded Protocol No. | Nil |
| Effective Date |
Table of contents :
| Sr. No. | Subject | Page No. |
| Protocol Approval | ||
| Objective | ||
| Scope | | |
| Responsibility | ||
| Product profile | ||
| Methodology | ||
| Verification parameters | ||
| Incident/Deviation | ||
| Summary/Final conclusion/Recommendation | ||
| Abbreviation | ||
| Revision History |
- Protocol Approval:
Prepared By:
| Functional Area | Name | Designation | Signature / Date |
| Quality Control |
Reviewed By:
| Functional Area | Name | Designation | Signature / Date |
| Quality Assurance | |||
| Head Quality Control |
Approved By:
| Functional Area | Name | Designation | Signature / Date |
| Head QA |
- Objective:
The objective of this protocol is to verify the suitability of Naproxen Ph. Eur. by considering thefollowing parameters:
| Parameters | Naproxen Ph. Eur. |
| Specificity | yes |
| Precision | |
| Method Precision | yes |
| Intermediate Precision | yes |
- Scope :
This protocol is applicable for the verification of assay of Naproxen Ph. Eur.
- Responsibility of Validation Team:
| Departments | Responsibilities |
| QC | Preparation & Review of Protocol. |
| Analysis of samples and recording of data. | |
| Compilation and Review of data | |
| Preparation of Summary Report. | |
| To impart training of protocol to concerned department/persons. | |
| QA | Review of protocol. |
| Co-ordination with QC to carryout Verification. | |
| Review of data and summary report. | |
| Head QA | Approval of Protocol |
- Product Profile:
| Category | Nonsteroidal Anti-inflammatory Drug (NSAID) | |
| Reason for Verification | First Verification | |
| Active Ingredient | Naproxen Ph. Eur. | |
| Method Reference | European Pharmacopoeia Reference document of Divi’s Laboratories limited | |
| Specification Limits | Assay (On Dried basis) | Between 99.0% and 101.0% w/w |
- Methodology:
- Assay
Chemical, reagents and filters:
Table 1.0: Chemical, reagents and filters
| Sr. No | Material /Chemicals/Filters | Grade |
| 1. | Sodium hydroxide (NaOH) | AR Grade |
| 2. | Methanol | HPLC Grade |
| 3. | Water | Milli Q Water/ HPLC water |
Diluent: Prepare a mixture of Methanol: Water (75:25).
Procedure: First perform blank run by taking 50 mL of mixture of methanol : water (75:25). Take 0.5 g of sample in titration vessel add 50 mL of mixture of methanol : water (75:25) stir for two minutes and then titrate with
0.1 N NaOH, potentiometrically by using Auto titrator. Calculate the assay on dried basis.
Calculation:
V x 0.02303 x 100 x C
——————————————————————-
0.1 X A
Each 1 ml of 0.1 M sodium hydroxide is equivalent to 23.03 mg of Naproxen.
Where,
V = volume of 0.1 M Sodium Hydroxide
C = Molarity of 0.1 M Sodium Hydroxide
A = weight of sample in g
Acceptance Criteria:
If the % Assay on dried basis is within the specification limit (Between 99.0 % and 101.0 %), then the material is deemed as passing this test.
- Loss on Drying
Procedure:
Weigh a glass-stopper shallow weighing bottle that has been previously dried at 105°C ± 2°C, cool to room temperature by keeping in desiccator then weigh. Transfer to the bottle the 1.000 g quantity of the sample, cover it and accurately weigh the bottle and the contents. Dry the substance at 105°C ± 2°C for 3 hours. After drying is completed open the drying chamber close the bottle promptly and allow it to cool to room temperature in a desiccator before weighing. Weigh the bottle and calculate the loss on drying using the given below formula:
Calculation:
Loss in weight (g) x 100
=—————————————————–
Weight of sample (g)
Requirement: As per current version of approved specification.
Analytical Parameters to be verified and acceptance criteria given below Table 2.0:
Table 2.0
| Sr. No. | Analytical Performance Parameter | Acceptance Criteria |
| 1. | Specificity | To check the Interference of the 0.1 M Sodium Hydroxide. |
| 2. | Method Precision | The assay values should be in between 99.0 % to 101.0 % on dried basis for all six determinations. The % RSD of six assay values should be NMT 2.0 for Naproxen Ph. Eur.. |
| 3. | Intermediate Precision (Ruggedness) | The assay values should be in between 99.0 % to 101.0 % on dried basis for all six determinations of second analyst and its %RSD should be NMT 2.0.The cumulative % RSD of assay values for both the analysts should NMT 2.0. |
- Verification parameters:
The following parameters to be perform for the verification activity.
Specificity
Method Precision
Intermediate
- Specificity:
Specificity of analytical method is its ability to assess unequivocally the analyte in presence of components that may be expected to be present in 0.1 M Sodium Hydroxide. Prepare blank solution without analyte and titrate as per methodology and check the interference and record the titrant value consume.
- Method Precision:
The precision of an analytical method is the degree of agreement among individual test results when the procedure is applied repeatability to multiple samplings of homogenous sample. It is usually expressed as the standard deviation and the relative standard deviation.
Prepare six individual sample of same batch and analyze as per methodology.
Calculate the % assay of Naproxen on dried basis and the % RSD of assay for six individual samples.
Acceptance Criteria: The assay should be between 99.0 per cent and 101.0 per cent on dried basis for all six determinations. The % RSD for assay of six individual samples should be NMT 2.0.
- Intermediate Precision ( Ruggedness ):
Intermediate Precision (Ruggedness) of an analytical method is the degree of repeatability of test results obtained by the analysis of same samples by different analyst on different days.
Note: The result obtained from method precision will be considered as the results of first analyst for comparison in ruggedness.
Intermediate precision is performed by analyzing a homogenous sample, by second analyst on second day by preparing six individual sample of same batch and analyze as per methodology. Calculate the % assay on dried basis and the % RSD of assay for six individual samples performed by second analyst.
Acceptance Criteria:
The assay should be between 99.0 per cent and 101.0 per cent on dried basis for all six determinations performed by second analyst. The % RSD for assay of six individual samples should be NMT 2.0.
The cumulative % RSD of assay for both the analysts is NMT 2.0.
- Incident /Deviation:
Any incident or deviation observed during analytical method verification should be recorded and investigation as per SOP.
- Summary/ Conclusion / Recommendation:
Final conclusion should be drawn from analytical method verification for its use to analyze the assay test of Naproxen Ph. Eur. by Autotitrator.
Summary of verification report shall be prepare and accordingly conclusion and recommendation to be given.
Abbreviation:
ASS : Assay
VERP : Verification Protocol
SD : Standard deviation
ml : Milliliter
mg : Milligram
min. : Minutes
QA : Quality Assurance
QC : Quality Control
% : Percentage
ºC : Degree centigrade
EP/Ph.Eur. : Europeian Pharmacopoeia
RSD : Relative standard deviation
NLT : Not less than
NMT : Not more than
g : Gram
V : Volume
M : Molarity
Revision History:
| Revision No. | Details of changes | Reason |
| 00 | Nil | New Document |
