Nitrosamine Analysis in Ranitidine Tablets

Introduction

Ranitidine has been withdrawn from many markets because of concerns about nitrosamine formation. NDMA and other nitrosamines can appear when ranitidine breaks down under certain conditions. These compounds are harmful, which is why testing became a priority during the investigations and recalls that followed.

Screening tablets for nitrosamines helps confirm whether degradation has taken place and whether levels fall within acceptable limits. GC-TEA provides a sensitive way to detect nitrosamines in ranitidine products and to assess changes that may occur during storage or under stress conditions.

This method uses gas chromatography with TEA detection to separate and quantify a range of nitrosamines, including NDMA and NDEA, in ranitidine tablets. It offers a clear approach for laboratories that need to monitor nitrosamine levels during testing.

The Challenge

Ranitidine degradation can lead to nitrosamine formation

Ranitidine is known to degrade over time, especially when exposed to heat or stored for long periods. This breakdown can create nitrosamines such as NDMA and NDEA. These compounds are harmful, and several investigations showed that nitrosamine levels in some ranitidine products increased as they aged.

Because degradation is not always predictable, different batches can show different levels of nitrosamines. Tablets that appear stable during manufacture can develop NDMA or NDEA later in storage. This uncertainty made it difficult for manufacturers to confirm whether products remained within acceptable limits.

Routine testing helps identify when nitrosamines are present and whether breakdown has taken place. To do this effectively, laboratories need a sensitive method that can separate the compounds clearly and detect them at low concentrations.

The Solution

GC-TEA provides a sensitive way to measure nitrosamines in ranitidine 

Gas chromatography with TEA detection gives laboratories a clear way to measure nitrosamines that may form as ranitidine degrades. The GC separates each compound, and the TEA detects the N–NO functional group, which is common to all nitrosamines. This makes it well suited to NDMA, NDEA, and related compounds.

Tablet extraction is simple. A weighed amount of crushed ranitidine tablets is mixed with methanol or another suitable solvent. The extract is filtered and injected into the GC-TEA for analysis. This preparation keeps the workflow consistent and reduces the chance of contamination during handling.

The method separates a broad set of nitrosamines, including NDMA and NDEA, under controlled GC conditions. The TEA provides stable baselines and distinct peak shapes, even when compounds are present at low levels. This helps laboratories identify when nitrosamines have formed and whether levels fall within acceptable limits.

Using GC-TEA allows manufacturers and laboratories to check ranitidine products with confidence. The method highlights samples that contain measurable nitrosamines and supports decisions about storage stability, batch evaluation, and further investigation.