New Test Method for Busulfan in Plasma Provides Rapid Analysis in Bone Marrow Patients


Mayo Clinic laboratorians have designed a more efficient and cost-effective method for the measurement of busulfan in the plasma of bone marrow patients—described in a recent paper published in Therapeutic Drug Monitoring. Busulfan, a chemotherapy drug used to remove human bone marrow cells of patients in preparation for allogenic hematopoietic stem cell transplantation, eliminates the malignant cells and provides immunosuppression while creating space for new stem cells.

Besides reducing costs of busulfan analysis by approximately five-fold, the new method also cuts the previous assay’s cycle time of 218 seconds (per injection for the quantitation of busulfan) down to a mere 20 seconds per sample.

Paul Jannetto, Ph.D.
Paul Jannetto, Ph.D.

“During treatment, the monitoring of this drug is done to optimize the dosage and achieve target therapeutic area under the curve (AUC) concentrations while minimizing serious adverse drug effects—particularly hepatic veno-occlusive disease—which can be life-threatening,” says Paul Jannetto, Ph.D., senior co-author of the study paper. “It’s a test that requires a fast turnaround time so clinicians can make a timely dosage adjustment if needed.”

To answer this urgent clinical need for a quicker turnaround time and increased testing volume, Mayo laboratorians validated an ultrafast online solid-phase extraction/tandem mass spectrometry (SPE-MS/MS) method. Prior methods for assaying busulfan could take up to four hours and used gas chromatography mass spectrometry (GC/MS) with derivatization. Remarkably, the new study method reduced turnaround times of busulfan testing from four hours to approximately one hour.

Loralie Langman, Ph.D.

Previous methods were more complicated and involved an extra sample preparation step (derivatization) that added labor, time, and cost. “We basically simplified the sample preparation process and used a rapid online solid-phase extraction/tandem mass spectrometry assay,” says Loralie Langman, Ph.D., also a senior co-author on the paper. “The new method has a broader analytical measuring range so we can quantitate the busulfan concentration the first time, as opposed to having to re-preparethe assay and dilute out the patient’s sample to get a result if it’s elevated.”

On a grand scale, the study met its goal of decreasing turnaround times to allow pharmacists and physicians to get results back faster and, if needed, adjust the dose before the next series begins. Thus, the amount of time a patient is getting high concentrations of the drug is limited and, theoretically, will reduce the chances of life-threatening toxicity.

The new process enhances labor and reagent savings via the removal of derivatization and repeat testing for dilutions, which allows technologists to use their time more efficiently.

“We’re reducing the cost of health care by offering a test that provides clinically relevant care in a timely fashion at an affordable price,” says Dr. Langman.

From here, Mayo laboratorians plan to refine the test. “Our future assay format will also be customizable,” says Dr. Jannetto, “allowing clinicians and institutions to set different collection time points, have different target AUCs, and use different dosing protocols (6-hour or 24-hour) so that this same test can be used for all these situations. And, with it, there will be an enhanced report with the AUC graph.”

Kelley Luedke

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.