SOP for Stability Study of Volumetric Solutions

SOP for Stability Study of Volumetric Solutions

1.0 Objective

To establish a standardized procedure for conducting stability studies of volumetric solutions to determine and assign their shelf life.

2.0 Scope

This SOP is applicable to all volumetric solutions prepared and used in the Quality Control Laboratory.

3.0 Responsibility

Chemist or above in the QC Laboratory shall be responsible for preparation, standardization, stability monitoring, documentation, and reporting.

4.0 Accountability

Head – Quality Control shall be accountable for implementation and compliance of this SOP.

5.0 Procedure

5.1 Preparation and Initial Standardization

5.1.1 Preparation, standardization, and storage of volumetric solutions shall be carried out as per the approved SOP and relevant General Test Procedure (GTP) or Pharmacopoeial method.
5.1.2 Initial standardization shall be performed on the same day or the following day of preparation.
5.1.3 Records of preparation and initial standardization shall be maintained.

5.2 Stability Study Design

5.2.1 For each volumetric solution, a set of three separate solutions shall be prepared for stability study.
5.2.2 Each solution shall be assigned a unique ID number.
5.2.3 The three solutions shall be labeled as:

• S-1/3

• S-2/3

• S-3/3

5.3 Standardization Frequency

All three volumetric solutions shall be standardized at the following intervals from the date of first standardization:

5.3.1 First Week (Alternate Days):

• 3rd Day

• 5th Day

• 7th Day

5.3.2 Second and Third Week (Every Three Days):

• 10th Day

• 13th Day

• 16th Day

5.3.3 Thereafter (Weekly for Three Weeks):

• 23rd Day

• 30th Day

• 37th Day

All observations and results shall be recorded in the Stability Study Summary Sheet.

5.4 Acceptance Criteria

5.4.1 At each interval:

• The solution strength shall not deviate by more than ±10% of the prescribed strength.

• Normality/Molarity shall be determined in triplicate.

• Relative Standard Deviation (RSD) shall be NMT 0.2%.

5.4.2 The Normality/Molarity at each interval shall not differ by more than ±0.2% from the initial (1st day) Normality/Molarity.

5.5 Shelf Life Determination Criteria

Shelf life shall be assigned based on the first failure observed:

• If failure occurs on 3rd, 5th, 7th, or 10th day → Shelf life = 1 day

• If compliant up to 10 days but fails on 13th or 16th day → Shelf life = 7 days

• If compliant up to 16 days but fails on 23rd or 30th day → Shelf life = 15 days

• If compliant up to 30 days but fails on 37th day → Shelf life = 25 days

• If compliant up to 37 days → Shelf life = 1 month

5.6 Final Shelf Life Assignment

5.6.1 If all three solutions (S-1/3, S-2/3, S-3/3) show the same shelf life, that shelf life shall be assigned.
5.6.2 If different shelf lives are observed, the minimum shelf life shall be assigned.

5.7 Handling of Abnormal Results

5.7.1 If at any interval one or more solutions fail to meet acceptance criteria, re-standardization shall be performed:

• By two different analysts

• In triplicate

5.7.2 The average of six values shall be calculated and reported.
5.7.3 If all six values meet the criteria, the stability study shall continue.
5.7.4 If any value fails, the stability study shall be discontinued and shelf life assigned accordingly.
5.7.5 All observations shall be documented in the Verification of Abnormal Results format.

5.8 Documentation and Display

5.8.1 A consolidated list of assigned shelf life for volumetric solutions shall be prepared.
5.8.2 The approved shelf life list shall be displayed in the QC Laboratory.

6.0 Annexures

1. Label of Volumetric Solution for Stability Study

2. Summary Sheet of Stability Study of Volumetric Solution

3. List of Shelf Life of Volumetric Solutions

4. Preparation and Standardization Format of Volumetric Solution

5. Verification of Abnormal Results Format

Annexure 1: Label of Volumetric Solution for Stability Study

Volumetric Solution – Stability Study

• Name of Volumetric Solution: ___________

• Volumetric Solution ID No.: ___________

• Volumetric Solution No.: S-1/3 / S-2/3 / S-3/3

Prepared By/Date: ___________
Checked By/Date: ___________

Annexure 2: Summary Sheet of Stability Study

• Name of Volumetric Solution: ___________

• Volumetric Solution ID No.: ___________

(Table including S-1/3, S-2/3, S-3/3 with Normality/Molarity, Standardized By/Date, Checked By/Date for each interval.)

Remarks (if any): ____________________

Conclusion: ____________________

Authorized By/Date: ___________

Annexure 3: List of Shelf Life of Volumetric Solutions

Prepared By: _______
Checked By: _______
Approved By: _______

(Signature/Date)

Annexure 4: Preparation and Standardization Format

Includes:

• Name of Volumetric Solution

• Batch No. of Chemical/Reagent

• Manufacturer

• Preparation Procedure

• Standardization data (Weight, Titre Volume in triplicate)

• Calculations

• Average Normality/Molarity

• RSD (NMT 0.2%)

• % Variation from 1st Day (NMT 0.2%)

• Analyst and Reviewer Signatures

Annexure 5: Verification of Abnormal Results

• Standardization performed by Analyst 1 (Triplicate)

• Standardization performed by Analyst 2 (Triplicate)

• Calculation of Average of Six Values

• % Variation from Initial Value

• Final Conclusion

• Checked By/Date