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J Pharm Biomed Anal. 2018 Feb 20;150:112-120. doi: 10.1016/j.jpba.2017.11.060. Epub 2017 Nov 28.

High throughput routine determination of 17 tyrosine kinase inhibitors by LC-MS/MS.

Author information

1
CHU de Bordeaux, Bordeaux, F-33000, France; Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, Team PHARMACOEPIDEMIOLOGY, UMR 1219, F-33000 Bordeaux, France.
2
CHU de Bordeaux, Bordeaux, F-33000, France.
3
CHU de Bordeaux, Bordeaux, F-33000, France; Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, Team PHARMACOEPIDEMIOLOGY, UMR 1219, F-33000 Bordeaux, France. Electronic address: stephane.bouchet@chu-bordeaux.fr.

Abstract

Several studies have shown that therapeutic drug monitoring of tyrosine kinase inhibitors (TKI) can improve their benefit in cancer. An analytical tool has been developed in order to quantify 17 tyrosine kinase inhibitors and 2 metabolites in human plasma (afatinib, axitinib, bosutinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, regorafenib, regorafenib M2, regorafenib M5, ruxolitinib, sorafenib, sunitinib, vandetanib). Drugs were arranged in four groups, according to their plasma concentration range: 0.1-200ng/ml, 1-200ng/ml, 4-800ng/ml and 25-5000ng/ml. Solid phase extraction was used and separation was performed with HPLC using a gradient system on a solid core particle C18 column (5×2.1mm, 1.6μm). Ions were detected with a triple quadrupole mass spectrometry system. This assay allows rapid determination of 19 TKI in less than 5min per run. This high throughput routine method will be useful to adjust doses of oral anticancer drugs in order to improve treatments efficacy.

KEYWORDS:

Mass spectrometry; Targeted anticancer therapy; Therapeutic drug monitoring; Tyrosine kinase inhibitors; Ultra high pressure liquid chromatography

PMID:
29220734
DOI:
10.1016/j.jpba.2017.11.060
[Indexed for MEDLINE]

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