An article published by Nick Verougstraete and Christophe P. Stove in the January 2022 issue of the Journal of Pharmaceutical and Biomedical Analysis, demonstrated a robust analytical validation of eight tyrosine kinase inhibitors (TKI) as potential candidates for TDM of cancer patients.
The paper is entitled “Volumetric absorptive microsampling as a suitable tool to monitor tyrosine kinase inhibitors.” It showcases development and validation of a robust extraction from samples collection on Mitra® devices based on VAMS® technology for use on a previously developed multiplex LC-MS/MS assay.
This assay was originally developed for liquid blood and plasma samples. The researchers proposed it as a possible alternative method to measure TKIs on dried blood where a previous study had shown a failure rate of 20% when dried blood spot (DBS) had been employed.
Tyrosine kinase inhibitors, or TKIs, are a class of anti-cancer drugs that target the tyrosine kinase group of enzymes, which act to phosphorylate up to 50 proteins. The phosphorylation effect acts in several ways to promote cancer formation, by switching on and off the function of certain proteins.
This leads to changes in physiological activities such as an increase in cellular influx of glucose, (the main fuel for cellular metabolism) and a reduction in cellular contact inhibition, which allows for tumors to proliferate.
TKIs inhibit this kinase activity, which helps to reduce inappropriate cellular growth and proliferation, making them an effective cancer treatment. The first TKI to be approved by the FDA was imatinib in 2001.
Since then, more than 20 tyrosine kinase inhibitors have been approved for treatment of cancers such as chronic myeloid leukemia and non-small cell lung cancer.
Currently, TKIs are not medications that are routinely monitored by therapeutic drug monitoring (TDM).
However, because TKIs have a narrow therapeutic index, they are ideal candidates for future TDM programs. Treatment adherence can be problematic with certain classes of anticancer drugs, and it is hoped that monitoring TKIs more closely will help to improve this.
With effective monitoring of TKIs in mind, the research group chose to use Mitra with VAMS over DBS for the following reasons:
As the COVID-19 pandemic enters its third year, it is imperative that research studies like this one are conducted to widen the scope of remote sampling across many analytes.
Due to the vulnerability of cancer patients, at-home monitoring of drug levels and biomarkers, is a sensible approach to reduce their risk of infection when traveling to clinics.
The study by Verougstraete and Stove demonstrated a robust method for remote monitoring of eight TKIs. Moreover, due to their experiences with other studies employing remotely collected Mitra-VAMS samples, Mitra devices would be an ideal platform for follow-up studies in this area of research.
This study paper was summarized for our readers by James Rudge, PhD, Neoteryx Technical Director. This is curated content. To learn more about the important research outlined in this review, visit the original article published in the Journal of Pharmaceutical and Biomedical Analysis.