Principle and Calibration of TOC (Total Organic Carbon) Analyzer

Principle

A TOC Analyzer measures the amount of carbon in organic compounds present in a sample. It is commonly used in pharmaceutical water systems (e.g., Purified Water, WFI) to monitor organic contamination.

1. Basic Concept

   • Total Organic Carbon (TOC) is calculated as:

     $$\text{TOC}=\text{Total Carbon (TC)}-\text{Inorganic Carbon (IC)}$$

   • Total Carbon (TC) = Organic + Inorganic carbon in the sample.

   • Inorganic Carbon (IC) = Carbon present in carbonates, bicarbonates, and dissolved CO₂.

2. Working Principle

   • Oxidation: Organic carbon in the sample is oxidized to CO₂ using one of the following:

     • UV/Persulfate Oxidation (common in pharma water testing)

     • High-Temperature Combustion (common in environmental analysis)

   • Detection: The generated CO₂ is measured by a non-dispersive infrared (NDIR) detector or conductivity detector.

   • The instrument first measures IC, then TC, and subtracts IC from TC to get TOC.

Calibration

1. System Suitability / Calibration Standards

• Standards:

  • Sucrose solution → for organic carbon standard (known carbon concentration).

  • Sodium Bicarbonate solution → for inorganic carbon standard.

• Procedure:

  • Run blank (TOC-free water).

  • Inject sucrose standard → check recovery.

  • Inject sodium bicarbonate standard → check IC measurement accuracy.

  • The instrument should recover both within ±15% of theoretical values.

2. Calibration Steps

1. Prepare standard solutions using TOC-free water.

2. Measure blank (baseline correction).

3. Measure TC using sucrose standard.

4. Measure IC using sodium bicarbonate standard.

5. The instrument auto-calculates TOC.

6. Validate recovery against acceptance criteria.

3. Regulatory Notes

• USP <643> and EP 2.2.44 specify TOC limits and system suitability requirements.

• Calibration is often done before initial use, after maintenance, or as per SOP schedule.

Key Points

• TOC limit for Purified Water / WFI = 500 ppb (per pharmacopeia).

• Oxidation efficiency is critical — incomplete oxidation leads to low TOC readings.

• Always use TOC-grade water for blanks and standards.