A sensitive and accurate liquid chromatography-tandem mass spectrometry method for quantitative determination of the novel hepatitis C NS5A inhibitor BMS-790052 (daclastasvir) in human plasma and urine.
A liquid-liquid extraction (LLE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods have been developed and validated for the quantification of BMS-790052 (daclastasvir) in human plasma and urine. The samples were extracted with methyl-t-butyl ether (MTBE) before analyzing by an API 4000 mass spectrometer which was operated in a multiple reaction monitoring (MRM) mode for detection of positively charged ions of BMS-790052 and its internal standard, ¹³C₁₀-BMS-790052. The standard curves ranged from 0.050 to 50.0 ng/mL for BMS-790052 in human plasma, and 1.00-1000 ng/mL in human urine. The intra-assay precision (%CV), based on four levels of analytical QCs (low, geometric mean, mid and high), was within 8.6%; inter-assay precision (%CV) was within 6.7% for both plasma and urine methods, and the mean assay accuracy (%Dev) was within ±3.0% for both plasma and urine methods. The ruggedness of this accurate, precise, and selective LLE-LC-MS/MS method has been demonstrated in the successful analysis of several thousand clinical study samples.
Bioanalytical Sciences, Bristol-Myers Squibb, Princeton, NJ, USA. hao.jiang@bms.com
Hao
H
Jiang
Jianing
J
Zeng
Hamza
H
Kandoussi
Yifei
Y
Liu
Xiaodong
X
Wang
Marc
M
Bifano
Laura
L
Cojocaru
John
J
Ryan
Mark E
ME
Arnold
D002219:Carbamates; D002853:Chromatography, Liquid / Q000379:methods*; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006526:Hepatitis C / Q000097:blood* / Q000652:urine*; D006801:Humans; D007093:Imidazoles / Q000097:blood* / Q000302:isolation & purification / Q000652:urine*; D059625:Liquid-Liquid Extraction; D011759:Pyrrolidines; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014633:Valine / Q000031:analogs & derivatives; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D014633:Valine; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C549273:daclatasvir