LC-MS-MS Determination of Cyclo{(2S)-2-amino-8-[(aminocarbonyl)hydrazono] decanoyl-1-l-tryptophyl-l-isoleucyl-(2R)-2-piperidinecarbonyl} a Novel Histone Deacetylase Inhibitor in Rat Serum |
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Authors: | Beom Soo Shin Deok Ki Hong Jong Hwan Kwak John Kim Sun Dong Yoo |
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Institution: | (1) College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Gyeongbuk, South Korea;(2) College of Pharmacy, Sungkyunkwan University, Suwon, Kyeonggi-do, South Korea;(3) Clinical Research, Hanmi Pharm. Co. Ltd, Seoul, South Korea |
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Abstract: | A rapid and sensitive liquid chromatography-tandem mass spectrometry assay was developed for the determination of a novel
histone deacetylase inhibitor, cyclo{(2S)-2-amino-8-(aminocarbonyl)hydrazono]decanoyl-1-l-tryptophyl-l-isoleucyl-(2R)-2-piperidinecarbonyl} (SD-2007), in rat serum. The mobile phase consisted of acetonitrile and ammonium formate
(10 mM) (85:15 v/v), and the flow rate was 0.25 mL min−1. Chromatographic separations were achieved by isocratic elution on a C18 column. Multiple reaction monitoring was based on the transition of m/z = 681.8 → 83.6 for SD-2007 and 372.1 → 176.1 for trazodone (internal standard). A linearity was observed over a concentration
range from 2 to 1,000 ng mL−1 (r
2 > 0.999), with the lower limit of quantification at 2 ng mL−1 with 100 μL of rat serum. The mean intra- and inter-day assay accuracy ranged from 98.5–109.7% to 95.2–102.7%, respectively,
and the mean intra- and inter-day precision was between 4.3–11.3% and 2.9–13.3%. The developed assay was applied to a pharmacokinetic
study of SD-2007 in rats after intravenous injection (dose 4 mg kg−1). |
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Keywords: | Column liquid chromatography-mass spectrometry LC-MS-MS Pharmacokinetics Histone deacetylase inhibitor SD-2007 |
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