Residue on Ignition (ROI) for Inorganic Impurities Determination

Pharmaceutical companies need to be certain that they are handling APIs of adequate quality. If a contaminated or adulterated batch of API is used in production, it can result in significant financial losses, production delays and reputational damage. Small-molecule API manufacturers are required to ensure the quality of all batches they produce by performing rigorous analysis. As a tyepe of classic gravimetric tests, residue on ignition (ROI) testing is a commonly used analytical method in batch release testing of small-molecule drugs. It is a back-weighing application used to determine the ratio of inorganic and organic components in samples. Certain information about the purity of the reagent is provided by collecting the precipitate or residue and drying or igniting it.

BOC Sciences has many years of experience in providing first-class analytical services for pharmaceutical and chemical samples and is a supplier of high quality testing and determination systems. Elemental microanalysis is an absolute necessity for any laboratory-based organisation and our main focus is to provide a dedicated service to our clients by utilizing the latest wet chemical analysis techniques and the wealth of experience we have gained over the years.

Principles of ROI

The sample is subjected to heat treatment in a drying oven under the influence of oxygen, thus destroying the organic substances. Mass loss (i.e. loss on ignition) represents the organic part of the sample. And residual ash (residue on ignition) represents the inorganic portion.

Our Methods - Wet Ashing

Pharmaceutical companies are responsible for ensuring that the drugs they sell are not only safe and effective for consumers, but are also consistent between batches and manufacturers; this involves measuring the ROI. The ROI% describes the amount of total concentration of inorganic salts and trace metals that fail to ignite at 600°C. Wet ashing is the treatment of the sample with a moderate amount of sulfuric acid prior to charring. The charring is done using an open flame. Liquid samples tend to foam. After the excess sulfuric acid is driven off, the sample will be muffled as above. It is a wet chemical method for measuring the amount of residual material that does not volatilized from a sample when a sample is ignited in the presence of sulfuric acid. In order to determine the amount of inorganic impurities in organic substances, BOC Sciences provides wet ashing testing according to the procedure described below.

• Step 1 Accurately weigh 1 to 2 grams of the substance in a suitable crucible that has been previously ignited at 600 ± 50°C for 30 minutes. Then, cool the sample in a desiccator, and weigh it
• Step 2 Moisten the sample with a small amount of sulfuric acid (usually 1 mL). Firstly, heat gently at a temperature as low as possible until the substance is thoroughly charred
• Step 3 Moisten the residue with a small amount (usually 1 mL) of sulfuric acid, heat gently until no more white smoke is produced, and ignite at 600 ± 50°C until the carbon is consumed
• Step 4 Ensure that no flame is produced at any time during the process
• Step 5 Cool the sample in the desiccator, weigh and calculate the percentage of residue
• Step 6 If the amount of residue obtained exceeds the limits specified in the monograph, repeat the moistening with sulfuric acid, heating and ignition as before, until a constant weight is reached or until the percentage of residue complies with the limits in the monograph

Figure 1. Illustration of the wet ashing used to determine the solubility of Pd. (Sugiyama, I. 2016)

Advantages of Our ROI Services

• Ability to decompose a large number of samples
• Low cost
• Low consuption of reagents
• Relatively safe
• Suitable for large-scale production