Is the calibration still holding? An internal standard plus a CRM as your QC

An internal standard keeps each run steady; a certified reference material tells you whether the steady answer is still right. Chart one, test the other, and watch both halves of accuracy.

By Medrado Analytical Innovations · Foundations, No. 19 · for the working analyst

Calibration ties an instrument to its standards so that the reference, not the instrument, decides the number. That is what makes two instruments agree and today's result comparable with last month's. But a calibration is a promise about the day it was made. Every run after that, two things can quietly change: the results can start to scatter, and the average can start to drift away from the truth. A lab can be precise and wrong (ten injections that agree to 0.5% can all be 4% low), or right on average and unreliable on any single day. Many routine QC charts watch only the first problem. This piece puts the two tools that watch both side by side, the internal standard and the certified reference material, and shows how they tell you whether the calibration is still holding.

Three words, used carefully

First, the vocabulary, because everyday lab speech blurs it. How much results scatter around their own average is precision. Whether that average is right is trueness, and its opposite, a systematic offset, is bias. In the international vocabulary, accuracy means both at once: a single result close to the true value needs good precision and good trueness.¹ An internal standard mostly helps precision. A certified reference material measures trueness. Together they tell you whether the calibration is still giving accurate results.

Part of the GC course

This lesson belongs to From signal to result, a course on the gas chromatograph from detector to reported number, coming soon. The rest of the lesson, its questions and the course run will be part of it.

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Check yourself

Answer in your head first, then open the answer. Any question can go into your Quiz me.

What does an internal standard correct?
Show the answer
“An internal standard divides out what affects analyte and internal standard alike; it cannot see what affects only one.”
See it in the article ·
Why can a certified reference material show bias when an in-house control sample cannot?
Show the answer
“A certified reference material is the one sample with an independently assigned value and a stated uncertainty, so it is the one that can show bias.”
See it in the article ·
How should the IS-corrected CRM result be used on the control chart?
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“Chart the result around your own average for stability; test that average against the certificate for bias.”
See it in the article ·

Glossary

Plain-language explanations, examples, where you would use each term, and the sources are in the full glossary.

Precision: How much results scatter around their own average.
Trueness: How close the average is to the true value; its opposite is bias.
Accuracy: In the international vocabulary, both at once: good precision and good trueness.
Certified reference material: A material with an independently assigned value and a stated uncertainty, traceable to a reference.

Sources

JCGM 200:2012, International Vocabulary of Metrology (VIM), 3rd ed., 2.13–2.15 and 2.18 (accuracy, trueness, precision, bias).
ISO 33403:2024, Reference materials: requirements and recommendations for use (replaces ISO Guide 33:2015).
T. Linsinger, ERM Application Note 1, "Comparison of a measurement result with the certified value", European Commission JRC (crm.jrc.ec.europa.eu).
Nordtest NT TR 569, Internal Quality Control: Handbook for Chemical Laboratories ("Troll book"), ed. 6 (2026), nordtest.info/wp/wp-content/uploads/2026/03/NT_TR_569_ed6_Eng.pdf.
ISO 7870-2:2023, Control charts, Part 2: Shewhart control charts.
ASTM D6299-26a (ASTM International, 2026), Standard Practice for Applying Statistical Quality Assurance and Control Charting Techniques to Evaluate Analytical Measurement System Performance.
US EPA, National Functional Guidelines for Organic Superfund Methods Data Review (internal-standard area and retention-time criteria for GC-MS).
W. Elbast et al., "European Bioanalysis Forum: recommendation for dealing with internal standard variability", Bioanalysis (2014).
US FDA, Evaluation of Internal Standard Responses During Chromatographic Bioanalysis: Questions and Answers, Guidance for Industry (September 2019), fda.gov/media/130451/download.
J. W. Dolan, "When should an internal standard be used?", LCGC North America (chromatographyonline.com).