title: Highly sensitive HPLC-DAD method for the assay of gefitinib in patient plasma and cerebrospinal fluid: application to a blood-brain barrier penetration study.
abstract: The quantification of intracranial gefitinib (GEF) exposure is limited owing to the sensitivity of analytical equipment. Although mass spectrometry (MS) is the preferred method because of its high sensitivity, the equipment is not available in many laboratories, especially in developing Asian countries. In this paper, we developed a highly sensitive high performance liquid chromatography-diode array detector (HPLC-DAD) method for the assay of GEF in human cerebrospinal fluid (CSF) and plasma. GEF was extracted from CSF and plasma by solid-phase extraction and liquid-liquid extraction, respectively. The chromatographic separation was performed on a C18 column with gradient elution of 0.1% triethylamine solution and acetonitrile, then finally detected at 344 nm. This method was validated and proved to be highly sensitive with a lower limit of quantitation value of 0.11 ng/mL in CSF and 11 ng/mL in plasma. The blood-brain barrier penetration ratio of GEF ranged from 1.48 to 2.41%. This method provides a reliable MS-independent solution for the quantitation of GEF in patients' CSF and plasma.
authors.affiliation: Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310022, China.|College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.|Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou, 310022, China.
authors.forename: Luo
authors.identifier: http://orcid.org/0000-0003-1187-4195
authors.initials: L
authors.lastname: Fang
authors.affiliation: Laboratory of Clinical Pharmacy, Zhejiang Cancer Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310022, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Weng
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Fanzhu
authors.initials: F
authors.lastname: Li
authors.affiliation: Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Hangzhou, 310022, China.|Department of Radiation Oncology, Zhejiang Cancer Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310022, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.|Institute for Individualized Medicine, Hangzhou First People's Hospital, Hangzhou, 310006, China.
authors.forename: Nengming
authors.initials: N
authors.lastname: Lin
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000077156:Gefitinib; D006801:Humans; D016014:Linear Models; D011799:Quinazolines / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction
chemical_list: D011799:Quinazolines; D000077156:Gefitinib
keywords: HPLC-DAD; cerebrospinal fluid; gefitinib; plasma; solid phase extraction