Surreal illustration of ammonia blood test impacting brain health

Is High Ammonia Making You Sick? Simple Steps to Improve Ammonia Testing Accuracy

Soraya Malik in Health & Wellness December 2025 • 5 min read.

"Discover how a modified blood test protocol can reduce errors and improve the reliability of ammonia level measurements, ensuring better diagnosis and treatment."

Ammonia, a natural byproduct of protein breakdown, can become toxic when levels rise too high in the body. This condition, known as hyperammonemia, can severely affect the brain and nervous system, leading to confusion, disorientation, and even coma [1]. Elevated ammonia levels often signal underlying issues such as liver or kidney disease, or inherited metabolic disorders that disrupt the body's ability to process nitrogen [1]. Recognizing and addressing hyperammonemia quickly is critical to preventing long-term damage.

Measuring ammonia levels accurately is challenging due to several factors that can influence the results. Issues like improper blood sample handling, delays in processing, and variations in testing methods can all lead to inaccurate readings [5]. Many clinical laboratories use the glutamate dehydrogenase method on automated platforms to measure ammonia, but these systems can sometimes produce error flags, indicating potential problems with the sample or the testing process. These errors can delay diagnosis and require repeat testing, adding to patient anxiety and healthcare costs.

To tackle these challenges, researchers at the Academic Medical Center in Amsterdam developed a modified protocol for ammonia testing on the Roche Cobas 8000 platform. This new approach, called the AMC NH3L adaptation, incorporates an additional step to pre-dilute the blood sample, aiming to reduce error flags and improve the reliability of ammonia measurements. By addressing the common pitfalls of ammonia testing, this adaptation promises to provide more accurate and timely results, ultimately enhancing patient care.

How Does Pre-Dilution Improve Ammonia Testing?

Surreal illustration of ammonia blood test impacting brain health

The standard method for measuring ammonia on the Roche Cobas 8000 platform involves directly analyzing a blood sample using the glutamate dehydrogenase method. However, a significant number of samples often trigger error flags due to absorbance limits being exceeded, a situation where the machine struggles to accurately read the sample [6]. This can happen for various reasons, including the presence of interfering substances in the blood, such as bilirubin (from jaundice) or lipids (from high cholesterol), which can distort the light passing through the sample during the measurement process.

The AMC NH3L adaptation addresses this issue by introducing a pre-dilution step. Before the sample is analyzed, it is automatically diluted four-fold with water within the instrument. This dilution reduces the concentration of not only the ammonia but also any interfering substances, bringing the absorbance levels within the acceptable range for the machine. By doing so, the adaptation aims to minimize the occurrence of error flags and provide a more accurate measurement of ammonia levels.

Here’s a breakdown of the key steps in the AMC NH3L adaptation:

Sample Collection: Blood is collected in pre-chilled EDTA tubes and immediately placed on ice to prevent ammonia levels from increasing.
Pre-Dilution: A 20 µl sample is automatically diluted with 60 µl of water within the Roche Cobas 8000 analyzer.
Analysis: The diluted sample is then analyzed using the glutamate dehydrogenase method, as in the standard protocol.
Result Reporting: The ammonia concentration is calculated, taking into account the dilution factor, to provide an accurate reading.

The researchers evaluated the effectiveness of the AMC NH3L adaptation by comparing it to the standard Roche method. They assessed several factors, including the frequency of error flags, the precision of the measurements, the correlation between the two methods, and the impact of interfering substances like hemolysis (ruptured red blood cells), icterus (jaundice), and lipemia (high levels of lipids) [7]. The results of these evaluations demonstrated that the AMC NH3L adaptation significantly reduced error flags and provided more reliable results, especially in samples with high ammonia concentrations or interfering substances.

A Simpler Test for Better Health

The AMC NH3L adaptation offers a practical solution to improve the accuracy and reliability of ammonia measurements in clinical laboratories. By incorporating a simple pre-dilution step, this modified protocol reduces error flags, minimizes the impact of interfering substances, and provides more consistent results [8]. This can lead to quicker and more accurate diagnoses of conditions associated with hyperammonemia, allowing for timely interventions and improved patient outcomes. For individuals at risk of high ammonia levels, this adaptation represents a significant step forward in ensuring reliable and effective monitoring.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.plabm.2018.e00115, Alternate LINK

Title: Improved Assay Protocol For Measurement Of Ammonia On The Roche Cobas 8000 Automated Platform

Subject: Clinical Biochemistry

Journal: Practical Laboratory Medicine

Publisher: Elsevier BV

Authors: J. Kaplon, J.J. De Groot, J.P. Van Straalen, M. Heckman, J.C. Fischer

Published: 2019-01-01

Everything You Need To Know

What is hyperammonemia, and why is it dangerous?

Hyperammonemia is a condition where ammonia levels in the body become excessively high. Ammonia is a natural byproduct of protein breakdown, but when levels rise too high, it can become toxic. This toxicity can severely impact the brain and nervous system, potentially leading to confusion, disorientation, and even coma. Recognizing and addressing hyperammonemia swiftly is crucial to prevent long-term neurological damage.

How does the AMC NH3L adaptation improve the accuracy of ammonia testing?

The AMC NH3L adaptation improves accuracy by incorporating a pre-dilution step. Before analysis on the Roche Cobas 8000 platform, the blood sample is automatically diluted four-fold with water. This dilution reduces the concentration of both ammonia and any interfering substances like bilirubin (from jaundice) and lipids (from high cholesterol). By lowering the concentration of these substances, the adaptation minimizes the occurrence of error flags and provides more accurate measurements of ammonia levels.

What is the glutamate dehydrogenase method, and how does it relate to ammonia testing?

The glutamate dehydrogenase method is the standard method used by many clinical laboratories on automated platforms to measure ammonia levels. It's a key component of the analysis performed on the Roche Cobas 8000 platform, where the AMC NH3L adaptation is applied. The method itself is used to measure the ammonia concentration in the diluted sample, taking into account the dilution factor to provide an accurate reading. It's a crucial step in the overall process of diagnosing and monitoring conditions related to high ammonia levels.

What are the key steps involved in the AMC NH3L adaptation protocol?

The AMC NH3L adaptation involves four key steps: 1. Sample Collection: Blood is collected in pre-chilled EDTA tubes and immediately placed on ice to prevent ammonia level increases. 2. Pre-Dilution: A 20 µl sample is automatically diluted with 60 µl of water within the Roche Cobas 8000 analyzer. 3. Analysis: The diluted sample is analyzed using the glutamate dehydrogenase method, as in the standard protocol. 4. Result Reporting: The ammonia concentration is calculated, considering the dilution factor, to provide an accurate reading.

What are the benefits of using the AMC NH3L adaptation in clinical laboratories?

The AMC NH3L adaptation offers several benefits. Primarily, it improves the accuracy and reliability of ammonia measurements by reducing error flags and minimizing the impact of interfering substances. This leads to more consistent results and can lead to quicker and more accurate diagnoses of conditions associated with hyperammonemia. This allows for timely interventions and improved patient outcomes. For individuals at risk of high ammonia levels, this adaptation represents a significant step forward in ensuring reliable and effective monitoring, therefore leading to better patient care.