title: Determination of vinblastine in tumour tissue with liquid chromatography-high resolution mass spectrometry.
abstract: There are virtually no analytical methods that describe determination of vinblastine and other vinca alkaloids in tumour tissue, albeit quantitative data on tumour drug amount is essential for maximal benefit of a particular anticancer treatment. The analytical method presented herein uses state-of-the-art sample preparation, separation and detection techniques to allow sensitive and selective determination of vinblastine in tumour tissue. After cryogenic grinding and sonication, tumour suspensions were extracted by Oasis MAX solid phase extraction and analysed for vinblastine with ultra-high performance liquid chromatography coupled to positive electrospray ionisation-high resolution mass spectrometric detection. The developed analytical method quantifies vinblastine down to 23 ng/g tumour tissue and shows satisfactory linearity (r(2)>0.99), precision (1.1-8.2%), accuracy (98%) and high selectivity with almost complete absence of matrix effects. The proposed method was found suitable to follow vinblastine levels in mice tumours and could be used to support preclinical pharmacologic studies.
authors.affiliation: Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia. Electronic address: tina.kosjek@ijs.si.
authors.forename: Tina
authors.initials: T
authors.lastname: Kosjek
authors.forename: Tanja
authors.initials: T
authors.lastname: Dolinšek
authors.forename: Darja
authors.initials: D
authors.lastname: Gramec
authors.forename: Ester
authors.initials: E
authors.lastname: Heath
authors.forename: Primož
authors.initials: P
authors.lastname: Strojan
authors.forename: Gregor
authors.initials: G
authors.lastname: Serša
authors.forename: Maja
authors.initials: M
authors.lastname: Čemažar
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification* / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005354:Fibrosarcoma / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D057230:Limit of Detection; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental; D012878:Skin Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D052616:Solid Phase Extraction / Q000379:methods*; D013010:Sonication; D021241:Spectrometry, Mass, Electrospray Ionization; D014747:Vinblastine / Q000008:administration & dosage / Q000302:isolation & purification* / Q000493:pharmacokinetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine
keywords: APCI; Analysis; FWHM; HRMS; LC; LOD; LOQ; Liquid chromatography; ME; MS; Mass spectrometry; QTOF MS; RE; RS; SPE; Solid phase extraction; Tumour; VBL; VCR; Vinblastine; WS; atmospheric pressure chemical ionisation; full width at half maximum; high resolution mass spectrometry; limit of detection; limit of quantification; liquid chromatography; mass spectrometry; matrix effect; quadrupole time-of-flight mass spectrometer; reconstitution solvent.; recovery; solid phase extraction; vinblastine; vincristine; wash solvent.