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Reference Solution – Preparation & Hold Time Study

Standard Operating Procedure (SOP) for Preparation, Handling and Hold Time Study of Reference Solution. In analytical chemistry, a standard solution is a solution containing a precisely known concentration of an element or a substance. A known weight of solute is dissolved to make a specific volume. It is prepared using a standard substance, such as a primary standard. Standard solutions are used to determine the concentrations of other substances

Handling of Reference Solution

1.0   PURPOSE:

    • The purpose of this SOP is to describe the procedure for preparation and hold time study and storage of reference solution.

2.0   SCOPE:

    • This SOP is applicable for preparation, hold time study and storage of reference solution used for analysis in Quality control department.Reference Solution

3.0   RESPONSIBILITY:

    • Analyst:
    • Preparation and use the solution as per defined procedure and specification.
    • Maintain all documents related to prepared solution.
    • Report any odd observations to section head during preparation and usage of solution (if observed).
    • To submit solution preparation raw data for checking to concern person.
    • Section Head:
    • To receive reference standard and impurity.
    • Allocate and handover the reference standard and impurity for preparation of solution to analyst
    • To ensure solution prepared only on calibrated instruments and as per respective analytical templates.

 4.0   PROCEDURE – REFERENCE SOLUTION :

    • General:

    • Use clean and dry glassware for preparation and storage of solution.
    • Preparation detail shall be recorded in the reference solution preparation record as in Annexure -5.

    • Precautions:

    • During preparation of reference solution check the validity of reference/working standard/impurity standard used for preparation.
    • Before preparation of reference solutions ensure the cleanliness of bottle or container used for storage purpose.
    • Use PPE’s such as nose mask, gloves, goggles etc. as per requirement during the handling of References standards, working standards and impurities.

    • Analysis:

    • Analyst shall prepare reference solutions as per pharmacopoeia or as specified in respective standard analytical procedure.
    • Fill the all details in annexure -5 and Hold time study protocol of solution respectively.
    • Assign the protocol no. for hold time study of solution as defined below: HTS/XX/YYY, where, HTS = Hold time study, XX=Last two digit of the year, YYY= Serial number for protocol. e.g. First protocol in the year of 2021 will be as : HTS/21/001.
    • Analyst shall prepare the reference solution study schedule as per Annexure -6,and
    • Mention all the analysis data and result in analyst work sheet.
    • Reference solution/hold time study solution shall be stored in clean and dry screw-capped glass bottle or in case of light sensitive solution use amber color bottle and reference solution container shall be stored in refrigerator / Cooling Cabinet.
    • The reference solutions for hold time study shall be labeled as RS For Hold time study as per Annexure -1.
    • Inject the RS as per respective analytical template initially and in the day interval of 15th, 30th, 45th, 60th, 75th , 90th and 105th day for hold time study of RS as per pharmacopoeia or as specified in respective standard analytical procedure and record the system suitability criteria in Hold time study report Annexure-9.

    • The frequency for the hold time study of solutions can be considered within the interval of + 5 days.

    • The solution prepared for the hold time study can also be used for the routine analysis and the data generated on the particular date can be considered for the hold time study purpose.
    • Whenever applicable prepare fresh reference solutions for use and label it and fill the necessary details as per Annexure-8.
    • Assign the batch No. to each solution, as defined below: RSol/XX/YYY/ZZ, where RSol= reference solution, XX=Last two digit of the year, YYY= serial number for each solution starting from 001, ZZ= Number of preparation. e.g for first reference solution of “X” product (for Assay test ) in year 2021 batch No. shall be assigned as RSol/21/001/01 and if same solution (for Assay test ) of “X” product will be prepared next time then batch No. of solution shall be as RSol/21/001/02 and for next product/test batch no. shall be as Rsol/21/002/01.
    • Write all the details Solution Storage Log Annexure -7.

    • List of reference solutions shall be prepared as per Annexure -3.

    • The reference solutions prepared from the reference standards/working standards/impurities shall be valid up to the system suitability criteria based on the hold time study.
    • If turbidity or haziness or any evidence of deterioration of solution appears in the solution before validity then such solutions shall be prepared freshly.
    • Acceptance criteria for the validity of reference solution :

    • System suitability parameters should be complies as per limit.

    • Each solution shall be clear and free from any sedimentation during entire Hold time study period.
    • Area of the main peak/chromatogram of the solution should not vary up to 10% from the initial area of that solution.
    • The solution which shall be used for TLC (for identification only), or resolution purpose, during the entire study the results should comply as per pharmacopoeia specification or in-house specification.
    • Validity days for solution shall be given based on hold time study data e.g.
      • If solution is stable up 105 days then assign the validity for 90 days and
      • If solution is stable up to 90 days then assign the validity for 75 days and so on.

Note : If sufficient quantity of reference standard / Working standard/Impurities is not available then weight of Reference standard /Working standard/ Impurities can be adjusted in such a manner so that final concentration of reference solution remains unchanged. e.g. If according to Analytical test procedure if 10 mg of X, reference standard is to be used in 100 ml volumetric flask then 2.5 mg of X, reference standard can be used in 25 ml volumetric flask.

5.0   ANNEXURES – REFERENCE SOLUTION:

Annexure -1 : Reference Solution For Hold time study

Solution For Hold time study
Reference solution for  
RS Batch No.  
Test  
Date of preparation  
Valid up to  
Prepared by ( Sign/ Date)  
Checked by (Sign/ Date)  

Annexure -2 : Batch numbering of reference solution

Sr. No.

 Product/Material Name Test Name of Solution

RS B. No.

Annexure -3 : List of reference solutions

Sr. No.

 Product/ Material Name Solution B. No. Name of  Solution Test Date of preparation Valid up to Prepared by Checked by

Remark

Annexure -4 : List of protocol for Hold time study of reference solution

Sr. No

 Protocol No. For Product/Material Date Test

Remark

Annexure -5 : Reference solution preparation record

Prepared for Product/Material :

Name of Reference Solution :

Test :

Reference Solution Batch No. :

Date of preparation:

Valid up to :

Prepared by:

Checked by:

Annexure -6 : Reference solution study schedule

Sr. No. Name of reference solution Product Name IH Code Protocol No. Initial 15 th day 30 th day 45th day 60th day 75th day 90th day 105th day Remarks

Annexure -7 : Solution Storage Log

Sr. No.

 Name of solution/solution Type and for (Product/Material) Solution code no. Reference Date of preparation Use before

Remarks

Annexure-8 : Reference solution label

RS for Routine use

Name of Material/Products   :

Name of  Solution :

Test                   :

Lot/ Batch No. Impurity :

Preparation Details :

Valid up to date:

Reference       :

Prepared by :                                     Date of preparation  :

Annexure-9 : Hold time study report of reference solution

Name of Reference Solution: Prepared By:
Product /Material Name:  Method No.:
Protocol no.: Number of impurities:
Test: Ref. Solution B.NO.:
Initial day Result

 

 Impurity Name B.NO./Lot No. of Impurity or Reference Standard Area(Limit-Area difference in % ±10 % of Initial area)
15th Day

 

 Impurity Name Area Area Difference in % Haziness/Turbidity
30th Day Impurity Name Area Area Difference in % Haziness/Turbidity
45th Day Impurity Name Area Area Difference in % Haziness/Turbidity
60th Day Impurity Name Area Area Difference in % Haziness/Turbidity
75th Day Impurity Name Area Area Difference in % Haziness/Turbidity
90th Day Impurity Name Area Area Difference in % Haziness/Turbidity
105th Day Impurity Name Area Area Difference in % Haziness/Turbidity

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Janki Singh is experienced in Pharmaceuticals, author and founder of Pharma Beginners, an ultimate pharmaceutical blogging platform. Email: [email protected]

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