UV or not UV: Nilotinib monitoring becomes affordable and accessible

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Ezine

  • Published: Jul 1, 2016
  • Author: Ryan De Vooght-Johnson
  • Channels: HPLC / UV/Vis Spectroscopy
thumbnail image: UV or not UV: Nilotinib monitoring becomes affordable and accessible

Peaks and troughs

The advent of tyrosine kinase inhibitors in the 1990s revolutionised the treatment of chronic myelogenous leukaemia, turning a once lethal form of blood cancer into one that can be managed with daily pills.

The advent of tyrosine kinase inhibitors in the 1990s revolutionised the treatment of chronic myelogenous leukaemia (CML), turning a once lethal form of blood cancer into one that can be managed with daily pills. Furthermore, because these drugs target the molecular aetiology driving the cancer cells, healthy cells are not exposed to the collateral damage associated with conventional chemotherapies. They work by blocking the genetic hallmark of CML—the newly fused Bcr–Abl hyperactive tyrosine kinase—preventing rogue leukemic cells from auto-firing their growth signals. Nilotinib is one such inhibitor.

A so-called second generation tyrosine kinase inhibitor, nilotinib is called upon when leukaemias evolve a resistance to the drug of first choice, imatinib. Patients, too, can benefit from nilotinib’s enhanced potency in blocking the ATP binding site of Bcr–Abl. However, their levels need to be meticulously monitored.

Reconnaissance

Current reconnaissance of nilotinib is expensive and inaccessible, Nakahara et al. explain, requiring ‘sophisticated high-cost equipment available only in a few specialised hospitals.’ In their paper published in the Journal of Clinical Laboratory Analysis, scientists from Oita University Hospital, Japan, set out to develop a more favourable method. This method, they claim, will be ‘simple, sensitive, rapid, and inexpensive,’ whilst also taking advantage of widely available equipment.

Their method is based on HPLC separation and UV-based detection. Following a quick sample clean-up with a solid-phase extraction cartridge, the innumerable plasma components are loaded onto a C18 silica solid phase and separated over an acidic acetonitrile/methanol mobile phase. Then, the nilotinib peaks eluted at 25 minutes are detected by UV light at 250 nm.

The test was put through its paces on plasma samples from 11 patients with CML who were being treated with nilotinib. Blood was drawn when nilotinib had dipped to its lowest trough—24 hours after their last pill, and immediately before their next dose.

Affordable and accessible

The HPLC-UV method demonstrated a broad dynamic range over 50 to 2500 ng/mL, and was capable of detecting down to 5 ng of nilotinib in a 1-mL drop of plasma. When tested at various times over the same and different days, measurements maintained precision. Most importantly, if the method is to be used to inform clinical practice, plasma samples spiked with mimic dosages of nilotinib were measured with 98 to 108% accuracy.

As well as measuring nilotinib levels with the new HPLC-UV method, the 11 plasma samples were also sent away for analysis by gold-standard LC-MS/MS. The authors present strong linearity between these measurements, adding gravitas for their case towards affordable and accessible nilotinib reconnaissance with HPLC-UV-based determination.

Could their test pave the way for widespread, intel-enhanced nilotinib regimens? Time will tell. The authors are putting it to the test in a prospective clinical trial.

Related Links

J. Clin. Lab. Anal., 2016. Nakahara et al., High-performance Liquid Chromatographic Ultraviolet Detection of Nilotinib in Human Plasma from Patients with Chronic Myelogenous Leukemia, and Comparison with Liquid Chromatography-Tandem Mass Spectrometry.

Article by Ryan De Vooght-Johnson

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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