NDMA Analysis in Metformin Tablets

Introduction

NDMA contamination has become a major concern in several pharmaceutical products, including metformin. NDMA is a probable human carcinogen, and regulators set strict daily limits to protect patients. For metformin, the acceptable limit is 96 ng per day, based on typical daily dosages of 500 mg to 2000 mg.

Screening tablets for nitrosamine content helps confirm that batches meet these limits before release. It also reduces the risk of recall, waste, and disruption across the supply chain. Automated Total Nitrosamine Analysis (ATNA) offers a fast way to check whether NDMA is present at measurable levels.

The ATNA system detects the NO functional group common to all nitrosamines. This makes it well suited for rapid screening of metformin samples, allowing laboratories to identify any batches that may contain elevated levels.

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The Challenge

NDMA can appear in metformin for several reasons

NDMA can form during the manufacture of metformin or during storage if certain conditions are present. Sources may include impurities in raw materials, reactions during synthesis, or degradation pathways that occur over time. Because these routes are not always predictable, contamination can appear in some batches while others remain unaffected.

Regulators set strict limits for NDMA in metformin tablets. The acceptable daily intake is 96 ng per day, which means even small amounts in a tablet can become a concern for higher-dose products. If NDMA is detected above this limit, batches may need to be held or discarded, leading to delays and added cost across the supply chain.

Screening tablets early helps avoid these issues, but traditional laboratory methods can take time and require specialist equipment. Manufacturers need a fast and reliable way to check whether NDMA is present at measurable levels before tablets move further through production.

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The Solution

A faster way to check metformin tablets for NDMA

Automated Total Nitrosamine Analysis provides a fast way to screen metformin tablets for NDMA. The system detects the NO functional group found in all nitrosamines, which makes it well suited for identifying NDMA at low levels before batches move further into production.

The workflow starts with a simple extraction step. A weighed portion of crushed metformin tablets is mixed with methanol and shaken to release any NDMA present. The extract is then filtered and placed directly into the system. No derivatisation or complex preparation is needed, which helps maintain repeatability and saves laboratory time.

Calibration curves for NDMA show clear, linear responses across a wide range of concentrations, and low-level standards produce clean, identifiable peaks. This gives laboratories confidence when checking if NDMA is present at measurable levels.

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By highlighting samples that contain NDMA, the system helps manufacturers avoid wasted batches, reduce delays, and maintain control over potential nitrosamine risks in metformin production.

Method Overview

How NDMA is analysed using automated total nitrosamine analysis

A small portion of metformin tablets is crushed and weighed. One gram of the crushed powder is mixed with 5 mL of methanol and shaken to extract any NDMA present. The extract is then filtered through a 0.45 µm PTFE filter and placed into a clean vial for analysis. This simple preparation helps maintain consistency and reduces the chance of contamination.

The ATNA system detects the NO functional group common to all nitrosamines. Calibration curves for NDMA show linear responses across a wide concentration range, with clear peaks even at low levels. This confirms that the system can identify NDMA at the levels relevant to metformin screening.

The workflow suits laboratories that need a fast way to screen batches of tablets. Automated handling reduces manual steps and supports repeatable measurements, making it easier to identify samples that require further investigation.

NDMA contamination in Metformin

Learn how NDMA became a concern in metformin products and how screening helps reduce the risk of contamination. This video explains the history behind recent findings, the conditions that can lead to NDMA formation, and the methods laboratories use to test for it.

Results and Reliability

What the analysis shows

Calibration curves for NDMA produced clear, linear responses across the full concentration range tested. Low-level standards generated well-defined peaks, and detector response remained stable throughout the sequence. This confirms that the system can identify NDMA at the levels relevant to metformin screening.

Repeatability was checked by injecting multiple replicates of the same concentration. Relative standard deviation remained low, showing that the workflow performs consistently when samples are prepared and analysed under the same conditions. The chromatograms showed clean baselines and sharp peaks, even at the smallest concentrations used in the study.

Extraction of metformin tablets produced detectable NDMA signals in spiked samples, with recoveries that matched expected values. This demonstrates that the extraction step and automated system can capture NDMA reliably from real tablet matrices.

This performance gives laboratories confidence when screening batches. The system highlights samples that may contain measurable NDMA and helps manufacturers decide which materials need further investigation before release.

Learn More

Get the full method and results

If you’d like to see the full details behind this testing method, you can download the complete application note. It includes chromatograms, calibration data, and the exact conditions used for the analysis. It’s a handy reference if you want to check your own setup or compare results.

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