Calibration of Total Organic Carbon Analyzer
Calibration of Total Organic Carbon (TOC) Analyzer
1. Introduction
A TOC analyzer is used in pharmaceutical water systems (e.g., Purified Water, WFI) to measure organic contamination. Calibration ensures the instrument accurately detects TOC levels in compliance with USP <643>, EP 2.2.44, and JP requirements.
2. Principle
TOC analyzers work by oxidizing organic carbon in a sample to CO₂, which is then detected (usually via NDIR – Non-Dispersive Infrared). Calibration is done using known standard solutions of sucrose (organic carbon source) and benzoquinone (system suitability test oxidizable compound).
3. Calibration Standards
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Sucrose Solution: 500 ppb carbon (prepared from certified reference material)
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Benzoquinone Solution: 500 ppb carbon (prepared from certified reference material)
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Blank: TOC-free water
4. Procedure
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Instrument Warm-Up: Allow TOC analyzer to stabilize as per manufacturer’s recommendations.
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Blank Test: Run TOC-free water to verify baseline stability.
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Span Calibration: Use sucrose standard to set the high point calibration.
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System Suitability Test (SST):
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Inject sucrose (500 ppb C) and record the response.
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Inject benzoquinone (500 ppb C) and record the response.
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Calculate % Recovery:
%Recovery=Response of BenzoquinoneResponse of Sucrose×100\% \text{Recovery} = \frac{\text{Response of Benzoquinone}}{\text{Response of Sucrose}} \times 100
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Acceptance criteria:
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Sucrose Recovery: 85–115%
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Benzoquinone Recovery: 85–115%
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Linearity Check: Test multiple concentrations (e.g., 100–1000 ppb) to verify linear response.
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Documentation: Record all results in the calibration logbook/SOP form.
5. Calibration Frequency
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Initial calibration before first use
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As per manufacturer’s recommendation (commonly quarterly or semi-annually)
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After maintenance or repairs
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When SST fails
6. References
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USP <643> – Total Organic Carbon
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EP 2.2.44 – Total Organic Carbon in Water for Pharmaceutical Use
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ICH Q7 – Equipment Calibration