title: Quantification of hydroxyurea in human plasma by HPLC-MS/MS and its application to pharmacokinetics in patients with chronic myeloid leukaemia.
abstract: Hydroxyurea (HU) has been used in the treatment of chronic myeloid leukaemia (CML) and other myeloproliferative malignancies. Considering patient's wide variation in clinical response to HU, a new and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to monitor patients' compliance to treatment and investigate the pharmacokinetics of HU in patients with CML. Stable isotope labeled HU-13C1,15N2was used as internal standard. Plasma samples were treated with acetonitrile to precipitate protein. The supernatant was injected directly without derivatization and separated on a hydrophilic interaction liquid chromatography column. HU was quantitatively analyzed with a mobile phase of acetonitrile-1.5mM ammonium formate (90:10, V:V) within 3min. The proposed method provided a linearity range of 1-200μg/mL. The coefficients of variation for intra- and inter-day precision were less than 2.07% and 4.28%, respectively, while the accuracy (bias) was in the range of -3.77 to 2.96%. This method was satisfactorily applied to the determination of HU in two patients with CML. It is suitable for supporting pharmacokinetic studies and clinical therapeutic monitoring.
authors.affiliation: Department of Pharmacy, The First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hai
authors.affiliation: Department of Pharmacy, The First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, The First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China.
authors.forename: Chunlu
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Hematology, The First Hospital, Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, 150001, China. Electronic address: zj_hmu@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000097:Acetonitriles / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D006918:Hydroxyurea / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood*; D057230:Limit of Detection; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D000097:Acetonitriles; D006918:Hydroxyurea; C032159:acetonitrile
keywords: Chronic myeloid leukaemia; Hydrophilic interaction liquid chromatography; Hydroxyurea; LC–MS/MS; Pharmacokinetics