Development and validation of an HPLC-MS/MS method to simultaneously quantify brigatinib, lorlatinib, pralsetinib and selpercatinib in human K2-EDTA plasma

  • Biomed Chromatogr. 2023 Mar 20;e5628. doi: 10.1002/bmc.5628.
J L Gulikers  1  2 ,  A J van Veelen  1  2  3 ,  E M J Sinkiewicz  1 ,  Y M de Beer  1 ,  M Slikkerveer  1 ,  L M L Stolk  1 ,  V C G Tjan-Heijnen  4 ,  L E L Hendriks  5 ,  S Croes  1  2 ,  R M J M van Geel  1  2
Affiliations
  • 1. Department of Clinical Pharmacy & Toxicology, Maastricht University Medical Centre, Maastricht, The Netherlands.
  • 2. CARIM School for Cardiovascular Disease, Maastricht University, Maastricht, the Netherlands.
  • 3. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
  • 4. Division Medical Oncology, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, the Netherlands.
  • 5. Department of Pulmonary Diseases, GROW - School for Oncology and Reproduction, Maastricht University Medical Centre+, Maastricht, the Netherlands.
PMID: 36941218 DOI: 10.1002/bmc.5628
Abstract

A liquid chromatography-tandem mass spectrometry method was developed and validated to quantify the small molecule inhibitors (SMIs) brigatinib, lorlatinib, pralsetinib and selpercatinib, which are used in patients with oncogenic driven non-small cell lung Cancer. Chromatographic separation was performed on a HyPURITY® C18 analytical column with a gradient elution using ammonium acetate in water and in methanol, both acidified with formic acid 0,1%. Detection and quantification were performed by a triple quad mass spectrometer with an electrospray ionization interface. The assay was validated over a linear range of 50 - 2,500 ng/mL for brigatinib, 25 - 1,000 ng/mL for lorlatinib, 100 - 10,000 ng/mL for pralsetinib, and 50 - 5,000 ng/mL for selpercatinib. All four SMIs were stable for at least seven days at cooling conditions (2 - 8 °C), and at least 24 hours at room temperature (15 - 25 °C) in K2-EDTA plasma. At freezing conditions (-20°C), all SMIs were stable for at least 30 days, except for the lowest quality control (QCLOW ) of pralsetinib. The QCLOW of pralsetinib was stable for at least 7 days at -20°C. This method provides an efficient and simple way to quantify four SMIs with a single assay in clinical practice.

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