The Laboratory Notebook

Answering important questions about quality.

By Robert Green

This month we try to give hope to a company that does not have all of the details about its product, which has been manufactured by a third party.

Q. I have a serious problem with the production of my product. I have used a manufacturer to produce my multi-component nutraceutical for three years, but now it appears they are going out of business. They helped me develop the product and I now realize I don’t have the exact formula they were using. I am trying to gather all the information I can from them so I can get my product manufactured elsewhere, but it is difficult. I am afraid that if I cannot get the information I need from them, I will not be able to replicate my product and therefore my business will be in trouble. Is there anything I can do to save my product (and me)?

A. Unfortunately, this scenario happens often and not just between manufacturers and their customers. We rely on other people to help us do the things that we cannot and sometimes the worst happens. In your case, the good news is that there is an analytical solution that can help you put the pieces of your product together; it is called a mass balance analysis.

A mass balance analysis employs highly specialized instrumentation to characterize the components comprising a product. If you are in a situation where the life of your product hangs in the balance (no pun intended), this is a good avenue to pursue with a skilled analytical laboratory. This type of analysis is similar to reverse engineering a product—something you might consider performing on a product that you suspect might be infringing on a patent you hold. This is not a study you would initiate unless there was a clear and present need for it, as it is time consuming and expensive.

So how does this work? It would be nice if there was one machine in which we could insert your product and out pops the formula. Nice, but not reality. Instead, there are several viable places to start. First, it is helpful if you give your lab a list of the major known components of your product and the quantities in which they exist. This is where routine analytical testing is highly beneficial. If you have been checking to make sure your product meets label claim on some or all components listed, you have a significantly higher likelihood of achieving a successful mass balance analysis in far less time and for far less cost. And here’s why: The first step of a mass balance analysis involves separating the components in the product. While there are several ways to do this, instrumentation involved in this effort generally includes high-performance liquid chromatography/mass spectrometry (usually referred to as LC/MS). This will allow the lab to generate data showing components in your product. Now unfortunately this is not as straightforward as it sounds. It’s not as simple as preparing the sample generically and running it on the instrument. In our last column (Nutraceuticals World, January/February 2007;10(1);28-29), we addressed the steps involved in method development and mentioned extraction and how that is an integral part of accurately analyzing any single component. The way the component is extracted from the product can dramatically affect the amount detected by the instrument if successfully detected at all. In general, when it comes to a mass balance analysis, the sample will be extracted and analyzed under standard conditions to start and the lab will deviate from there.

Now, at this phase it is a crapshoot. Like with all method development, the first few tries with extraction and chromatography may work great. The number of components expected may be detected. However, if this is not the case, further method development may be necessary to improve extraction and/or the chromatographic conditions. As you can imagine, without any existing data on a product this could sap significant time and resources. By knowing at least a few components in the product and the amounts at the beginning of a mass balance analysis, the laboratory will have a good place to start.

Alongside LC/MS analysis could also be gas chromatography/mass spectrometry (GC/MS) analysis to aid in identification. Just like LC/MS, extraction procedures and chromatographic conditions are highly variable so much experimentation may be required.

Both LC/MS and GC/MS can provide a comparative analysis, matching the detected spectrum of the components to a database of compounds, thus identifying it or the family of compounds it belongs to. Since every database includes a finite number of compounds, there is always the chance that something detected will not be matched. Again, the more data there is on the product to begin with, the more precise and efficient this step becomes.

To detect metals and minerals present in the product, we would turn to our ICP-MS. This can generate a straightforward analysis of these components with identification and quantification. With a highly sophisticated instrument like an ICP-MS, it is highly effective in this particular type of project.

So this is the beginning of a mass balance analysis. There is the extreme likelihood that things could get much more complicated, and with that may come added expense. The project may require additional instrumentation and more detailed method development to fully characterize the components of the product. The more experience your lab has with this type of work, the more likely the project is to succeed.

The moral of this story is make sure you know your product and act before there is a problem. The second lesson is you are never alone, especially with a good laboratory behind you. You have more reasons than ever to perform routine testing on your products. The larger the portfolio of data on your product, the easier it is to avoid potentially serious problems.NW