Implementing Mass Spectrometry in the Clinical Lab

When we brought liquid chromatography-tandem mass spectrometry (LC-MS/MS) testing into our lab, only I had direct experience in mass spectrometry. I had been working with LC-MS/MS for approximately 2 years and had developed an assay for 25-hydroxy­vitamin D and another for opioid and opiate analysis. In our section, we have a senior supervisor, a supervisor, two specialists, and the medical technologists. To date, we have trained the supervisor, two specialists, and one medical technologist to run the LC-MS/MS system—it is not a bench that everyone rotates on like the other benches. During training, I explained the components of the system and how they function, the maintenance schedule, and some of the unique qualities of this technology. I emphasized that LC-MS/MS requires high-quality solvents and reagents, the necessity of adding an internal standard immediately and accurately to each sample, and some intricacies of the software—by far the biggest challenge to a new user. During training, the technologists observed me complete each procedure, and then I observed them until we were all comfortable that each person was ready to work alone. I underscored the fact that it is very difficult to break the instrument, acknowledging that it can be a very intimidating piece of equipment.

How did you justify your LC-MS/MS purchase?

There were two main reasons for bringing LC-MS/MS into our lab: to improve turnaround time and to save money, as we were sending a large number of samples to reference laboratories. The most challenging part of preparing a return on investment (ROI) calculation was determining everything that was required to set up the lab. Many factors were not obvious, such as electrical work, ducts for proper venting, and reconfiguring existing cabinets.

The most helpful resources in this situation were the vendors’ site planning guides. Talking to the service engineers who actually install the instruments was also invaluable. I would caution others not to overlook the service contract charge covering both the LC and the MS in the cost calculations, as it is significant. It was also challenging to estimate the cost of the reagents and consumables for each assay we planned on developing, without knowing exactly which LC method and what type of extraction we would perform. Our approach was to review the literature to identify common methods, as well as talk with applications specialists from the MS companies.

Our administration required that we obtain quotes from three vendors of comparable LC-MS/MS systems, including the service contract, as well as a written justification for choosing the instrument that we picked.

What was your process for selecting an instrument?

First, we developed a list of questions to ask each of the four vendors under consideration, including all the technical requirements such as space, venting, electrical, as well as questions about the sensitivity for the analytes we wanted to measure—specifically at that time 25-hydroxyvitamin D, total testosterone, and estradiol. We also asked about service in our area—how quickly would they guarantee a service engineer would be on-site if we had a problem—as well as references of other clinical laboratories using their instruments with whom we could speak.

The second step was narrowing the choice from four to two vendors. We sent each vendor serum samples from pediatric patients so that they had to extract these samples and then quantify the total testosterone in them. We picked pediatric samples since they were the samples that we were going to run on the LC-MS/MS assay when we developed it in our lab. To be honest, making the final choice between these two vendors was one of the hardest decisions I’ve had to make. Not much separated the two instruments as far as sensitivity was concerned, and the overall list of pros and cons for each instrument/vendor combination was different, but comparable.

It took a wise friend to sit me down before I made my decision and say, “whatever instrument you pick, you’ll make it work.” In the end, we purchased the instrument from the vendor with whom I had the most experience. We knew what kind of service we could expect, and that the applications specialists were very hands-on and experienced with the assays we planned to develop. Now, 4 years on I’m happy to say I do not regret my decision.

How did installation compare to an automated chemistry analyzer?

In our laboratory, we had to install new electrical outlets (220 volt, 30 amp circuits) and install new ducts to vent the instrument. We also decided to buy a nitrogen generator bench and have the air compressor separate to keep the noise in the lab to a minimum. Placing the air compressor in another room required copper piping to pump the air from the air compressor to the nitrogen generator bench. We also had to get cabinets removed from the floor in order to fit the MS and the nitrogen generator bench, and from above the bench to make space for the LC system. 

Importantly, these instruments are large and heavy, so we discovered that it is important to know how to get them in your lab. Is the door frame large enough? Are pallets and pallet jacks allowed in your building (they are not in ours)? If not, who is going to volunteer to lift the mass spec without dropping it? The instrument also took up more space than we had imagined. Not just the footprint, but space for carrying out sample preparation and storing calibrators and quality control materials. In addition, a multi-tube vortex, or a piece of dry-down equipment, each need space and add other requirements, such as a nitrogen supply and fume hood. 

Finally, interfacing the LC-MS/MS to a laboratory information system can be costly and tedious. We are very lucky to have great information technology support, so we did not need to purchase an interface. A word of caution: the cost of interfacing should be included in an ROI calculation. Overall, the process took far longer than I expected. From the time we started to look at systems to our LC-MS/MS installation took over a year; developing and clinically validating the first assay took nearly another year. However, 4 years after purchase, I’m pleased to report that our laboratory administration and physicians are very satisfied with our LC-MS/MS results, and we’ve met our goals for reducing send-out costs and turn-around time.

I’ll describe our experience with method development and validation in the next issue of CLN’s Focus on Mass Spectrometry.

CLN's Focus on Mass Spectrometry is sponsored by Waters Corporation.