Ryosuke Nakahara1, Yuhki Satho2, Hiroki Itoh2. 1. Department of Clinical Pharmacy, Oita University Hospital, Yufu City, Japan. ryosuke-n@oita-u.ac.jp. 2. Department of Clinical Pharmacy, Oita University Hospital, Yufu City, Japan.
Abstract
BACKGROUND: A method for determining nilotinib concentration in human plasma is proposed using high-performance liquid chromatography and ultraviolet detection. MATERIALS & METHODS: Nilotinib and the internal standard dasatinib were separated using a mobile phase of 0.5% Na2 PO4 H2 O (pH 2.5)-acetonitrile-methanol (55:25:20, v/v/v) on a Capcell Pak C18 MG II column (250 × 4.6 mm) at a flow rate of 1.0 ml/min, and ultraviolet measurement at 250 nm. RESULTS: The calibration curve exhibited linearity over the nilotinib concentration range of 50-2,500 ng/ml at 250 nm, with relative standard deviations (n = 5) of 7.1%, 2.5%, and 2.9% for 250, 1,500, and 2,500 ng/ml, respectively. The detection limit for nilotinib was 5 ng/ml due to three blank determinations (ρ = 3). CONCLUSION: This method was successfully applied to assaying nilotinib in human plasma samples from patients with chronic myelogenous leukemia. In addition, we compared the results with those measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at BML, Inc. (a commercial laboratory). A strong correlation was observed between the nilotinib concentrations measured by our high-performance liquid chromatographic method and those obtained by LC/MS-MS (r2 = 0.988, P < 0.01).
BACKGROUND: A method for determining nilotinib concentration in human plasma is proposed using high-performance liquid chromatography and ultraviolet detection. MATERIALS & METHODS: Nilotinib and the internal standard dasatinib were separated using a mobile phase of 0.5% Na2 PO4 H2 O (pH 2.5)-acetonitrile-methanol (55:25:20, v/v/v) on a Capcell Pak C18 MG II column (250 × 4.6 mm) at a flow rate of 1.0 ml/min, and ultraviolet measurement at 250 nm. RESULTS: The calibration curve exhibited linearity over the nilotinib concentration range of 50-2,500 ng/ml at 250 nm, with relative standard deviations (n = 5) of 7.1%, 2.5%, and 2.9% for 250, 1,500, and 2,500 ng/ml, respectively. The detection limit for nilotinib was 5 ng/ml due to three blank determinations (ρ = 3). CONCLUSION: This method was successfully applied to assaying nilotinib in human plasma samples from patients with chronic myelogenous leukemia. In addition, we compared the results with those measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at BML, Inc. (a commercial laboratory). A strong correlation was observed between the nilotinib concentrations measured by our high-performance liquid chromatographic method and those obtained by LC/MS-MS (r2 = 0.988, P < 0.01).
Authors: Richard A Larson; Brian J Druker; Francois Guilhot; Stephen G O'Brien; Gilles J Riviere; Tillmann Krahnke; Insa Gathmann; Yanfeng Wang Journal: Blood Date: 2008-02-06 Impact factor: 22.113
Authors: Ellen Weisberg; Paul W Manley; Werner Breitenstein; Josef Brüggen; Sandra W Cowan-Jacob; Arghya Ray; Brian Huntly; Doriano Fabbro; Gabriele Fendrich; Elizabeth Hall-Meyers; Andrew L Kung; Jürgen Mestan; George Q Daley; Linda Callahan; Laurie Catley; Cara Cavazza; Mohammad Azam; Azam Mohammed; Donna Neuberg; Renee D Wright; D Gary Gilliland; James D Griffin Journal: Cancer Cell Date: 2005-02 Impact factor: 31.743