title: A rapid MCM-41 dispersive micro-solid phase extraction coupled with LC/MS/MS for quantification of ketoconazole and voriconazole in biological fluids.
abstract: A rapid dispersive micro-solid phase extraction (D-μ-SPE) combined with LC/MS/MS method was developed and validated for the determination of ketoconazole and voriconazole in human urine and plasma samples. Synthesized mesoporous silica MCM-41 was used as sorbent in d-μ-SPE of the azole compounds from biological fluids. Important D-μ-SPE parameters, namely type desorption solvent, extraction time, sample pH, salt addition, desorption time, amount of sorbent and sample volume were optimized. Liquid chromatographic separations were carried out on a Zorbax SB-C18column (2.1 × 100 mm, 3.5 μm), using a mobile phase of acetonitrile-0.05% formic acid in 5 mm ammonium acetate buffer (70:30, v/v). A triple quadrupole mass spectrometer with positive ionization mode was used for the determination of target analytes. Under the optimized conditions, the calibration curves showed good linearity in the range of 0.1-10,000 μg/L with satisfactory limit of detection (≤0.06 μg/L) and limit of quantitation (≤0.3 μg/L). The proposed method also showed acceptable intra- and inter-day precisions for ketoconazole and voriconazole from urine and human plasma with RSD ≤16.5% and good relative recoveries in the range 84.3-114.8%. The MCM-41-D-μ-SPE method proved to be rapid and simple and requires a small volume of organic solvent (200 μL); thus it is advantageous for routine drug analysis.
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia.|Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Pulau Pinang, Malaysia.
authors.forename: Noorfatimah
authors.initials: N
authors.lastname: Yahaya
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia.|Centre for Sustainable Nanomaterials, Ibnu Sina Institute for Scientific and Industrial Research, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia.
authors.forename: Mohd Marsin
authors.initials: MM
authors.lastname: Sanagi
authors.affiliation: Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, Selangor, Malaysia.
authors.forename: Noorizan
authors.initials: N
authors.lastname: Abd Aziz
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia.|Centre for Sustainable Nanomaterials, Ibnu Sina Institute for Scientific and Industrial Research, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia.
authors.forename: Wan Aini
authors.initials: WA
authors.lastname: Wan Ibrahim
authors.affiliation: Centre for Sustainable Nanomaterials, Ibnu Sina Institute for Scientific and Industrial Research, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia.
authors.forename: Hadi
authors.initials: H
authors.lastname: Nur
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia.|School of Marine and Environment Sciences, Universiti Malaysia Terengganu, Kuala Terengganu, Malaysia.
authors.forename: Saw Hong
authors.initials: SH
authors.lastname: Loh
authors.affiliation: Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, Johor Bahru, Johor, Malaysia.|Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
authors.forename: Sazlinda
authors.initials: S
authors.lastname: Kamaruzaman
mesh_terms: D000935:Antifungal Agents / Q000097:blood* / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000191:economics / Q000379:methods; D006801:Humans; D007654:Ketoconazole / Q000097:blood* / Q000652:urine*; D057230:Limit of Detection; D012822:Silicon Dioxide / Q000737:chemistry; D052617:Solid Phase Microextraction / Q000191:economics / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000191:economics / Q000379:methods; D065819:Voriconazole / Q000097:blood* / Q000652:urine*
chemical_list: D000935:Antifungal Agents; C509968:MCM-41; D012822:Silicon Dioxide; D065819:Voriconazole; D007654:Ketoconazole
keywords: LC/MS/MS; MCM-41; dispersive micro-solid phase extraction; ketoconazole; voriconazole