Validation of a chiral LC-MS/MS-ESI method for the simultaneous quantification of darolutamide diastereomers in mouse plasma and its application to a stereoselective pharmacokinetic study in mice

2018 ◽  
Vol 32 (5) ◽  
pp. e4173 ◽  
Author(s):  
Narayanan Balaji ◽  
Suresh P. Sulochana ◽  
Neeraj Kumar Saini ◽  
Siva Kumar A ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Mouse Plasma ◽  
Simultaneous Quantification ◽  
Chiral Lc

scholarly journals A new selective, and sensitive method for the determination of lixivaptan, a vasopressin 2 (V2)-receptor antagonist, in mouse plasma and its application in a pharmacokinetic study

2018 ◽  
Vol 16 (1) ◽  
pp. 614-620
Author(s):  
Haitham Alrabiah ◽  
Mohammed Abunassif ◽  
Sabry Attia ◽  
Gamal Abdel-Hafiz Mostafa
Keyword(s):  
Receptor Antagonist ◽  
Pharmacokinetic Study ◽  
Limit Of Detection ◽  
Internal Standard ◽  
Hplc Method ◽  
Maximum Plasma ◽  
Mouse Plasma ◽  
V2 Receptor ◽  
V2 Receptor Antagonist

AbstractA new, selective and sensitive HPLC method for the determination of lixivaptan, an oral selective vasopressin 2 (V2)-receptor antagonist, was investigated and validated. A Waters symmetry C18 column was used as a stationary phase in isocratic elution mode using a mobile phase composed of KH2PO4 (100 mM)-acetonitrile (40: 60, v/v) at a flow rate of 1.5 mL min-1. Diclofenac was used as the internal standard (IS). Lixivaptan and the IS were extracted from plasma by protein precipitation and were detected at 260 nm. Lixivaptan and diclofenac were eluted at 3.6 and 6.2 min, respectively. The developed method showed good linearity over the calibration range of 50 -1000 ng mL-1 with a lower limit of detection of 16.5 ng mL-1. The extraction percentage of lixivaptan in the mouse plasma was in the range of 88.88 - 114.43%, which indicates acceptable extraction. The aforementioned method was validated according to guidelines of the International Council on Harmonization (ICH). The intra- and inter-day coefficients of variation did not exceed 5.5%. This method was presented to be simple, sensitive, and accurate and was successfully adapted in a pharmacokinetic study of the profile of lixivaptan in mouse plasma. A mean maximum plasma concentration of lixivaptan of 113.82 ng mL-1 was achieved in 0.5 h after oral administration of a 10 mg kg-1 dose in mouse as determined using the developed method.

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