SOP for Development of Conductivity-Based Analytical Methods in AMD Laboratory

Department	Analytical Method Development
SOP No.	SOP/AMD/066/2025
Supersedes	SOP/AMD/066/2022
Page No.	Page 1 of 14
Issue Date	19/05/2025
Effective Date	20/05/2025
Review Date	19/05/2026

1. Purpose

This SOP defines the systematic procedure for the development and validation of analytical methods based on electrical conductivity. These methods are used for evaluating the ionic strength, purity, and quality of pharmaceutical substances and formulations.

2. Scope

This SOP is applicable to the Analytical Method Development (AMD) department for both qualitative and quantitative analysis of electrolytes, ionic excipients, and API solutions. It is especially applicable for water analysis, buffer systems, and ionic APIs.

3. Responsibilities

• Analytical Chemist: Responsible for conducting method development, performing measurements, documenting results, and preparing validation reports.
• Reviewer: Ensures test data integrity, verifies instrument calibration, and checks report completeness.
• QA Officer: Reviews compliance with GMP and regulatory requirements.
• Head – AMD: Approves the validated conductivity method for routine and regulatory use.

4. Accountability

The Head of Analytical Method Development is accountable for accuracy, regulatory compliance, and timely approval of the developed method.

5. Procedure

5.1 Principle of Conductivity Measurement

1. Conductivity is the ability of a solution to conduct electric current, which is directly proportional to the concentration and mobility of ions present.
2. Measurements are expressed in microSiemens per centimeter (µS/cm) or milliSiemens per centimeter (mS/cm).
3. Conductivity readings vary with temperature and must be corrected using a temperature compensation factor or by measuring at standard conditions (25°C).

5.2 Instrumentation and Calibration

1. Use a calibrated conductivity meter with digital temperature compensation, preferably equipped with:
   • Temperature sensor (integrated or external)
   • Glass or graphite conductivity cell (cell constant known)
2. Calibrate the instrument daily using certified standard solutions (e.g., 84 µS/cm, 1413 µS/cm, 12.88 mS/cm).
3. Record instrument ID, calibration date, and standard lot number in Annexure-1: Instrument Calibration Log.

5.3 Sample Preparation

1. Prepare solutions using conductivity-grade or deionized water.
2. Avoid use of glassware previously exposed to ionic detergents or residues.
3. Degas the sample if needed to remove CO₂ interference.
4. Ensure temperature equilibration before measurement.
5. Document preparation and any dilution factor in Annexure-2: Sample Preparation Log.

5.4 Measurement Procedure

1. Turn on the conductivity meter and allow to stabilize as per manufacturer’s guidelines.
2. Rinse probe with deionized water and blot dry with lint-free tissue.
3. Immerse the probe into the sample ensuring adequate coverage of electrodes.
4. Allow the temperature reading to stabilize at 25°C before recording the conductivity.
5. Repeat the measurement in triplicate and calculate the average.
6. Record all readings in Annexure-3: Conductivity Observation Sheet.

5.5 Calculation

Average Conductivity (µS/cm) = (Reading 1 + Reading 2 + Reading 3) / 3

If required, apply dilution correction and report in terms of original concentration.

5.6 Method Optimization

1. Evaluate:
   • Effect of temperature variation on conductivity
   • Stability of sample over time
   • Concentration-dependent linearity
2. Develop calibration curve using standard solutions to verify instrument response.
3. Document optimization studies in Annexure-4: Method Optimization Record.

5.7 Method Validation

1. Specificity: Confirm that only ionic species influence conductivity readings.
2. Linearity: Validate from low to high concentrations (R² ≥ 0.999).
3. Accuracy: Perform spike recovery studies at 80%, 100%, and 120% concentration levels.
4. Precision: Assess repeatability and intermediate precision (RSD ≤ 2.0%).
5. Robustness: Evaluate variation in sample volume, temperature ±2°C, and electrode rinsing method.
6. Summarize all findings in Annexure-5: Validation Summary Sheet.

6. Abbreviations

• SOP: Standard Operating Procedure
• AMD: Analytical Method Development
• RSD: Relative Standard Deviation
• µS/cm: MicroSiemens per centimeter
• mS/cm: MilliSiemens per centimeter

7. Documents

1. Instrument Calibration Log – Annexure-1
2. Sample Preparation Log – Annexure-2
3. Conductivity Observation Sheet – Annexure-3
4. Method Optimization Record – Annexure-4
5. Validation Summary Sheet – Annexure-5

8. References

• USP <645> – Water Conductivity
• EP 2.2.38 – Conductivity
• ICH Q2(R1) – Validation of Analytical Procedures
• IS 3025 (Part 14): Method of Measurement of Conductivity

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Instrument Calibration Log

Instrument ID	Standard Used	Measured Value	Acceptance Limit	Status	Checked By
COND-021	1413 µS/cm	1412 µS/cm	1410–1416	Pass	Sunita Reddy

Annexure-2: Sample Preparation Log

Sample Code	Solvent	Dilution	Temp	Prepared By
API-2025	Water	1:5	25°C	Rajesh Kumar

Annexure-3: Conductivity Observation Sheet

Trial	Conductivity (µS/cm)	Temperature	Average	Status
1	142.3	25.1°C	142.4	Pass
2	142.5	24.9°C
3	142.4	25.0°C

Annexure-4: Method Optimization Record

Parameter	Variation	Observation	Conclusion
Temperature	±2°C	±3.5% change in reading	Use temperature compensation

Annexure-5: Validation Summary Sheet

Parameter	Criteria	Result	Status
Accuracy	98–102%	99.1%	Pass
Precision	RSD ≤ 2.0%	0.85%	Pass
Linearity	R² ≥ 0.999	0.9993	Pass

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Expanded optimization and validation for high-conductivity buffers	Annual Review