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A novel,fast,sensitive and robust method based on ultra-performance liquid chromatography coupled to atmospheric pressure electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) has been developed to separate two Tibolone stereoisomers i.e.,3α-Hydroxy Tibolone and 3β-Hydroxy Tibolone and to quantify 3α-Hydroxy Tibolone using p-toulenesulfonyl isocyanate (PTSI) as a derivatizing reagent in human plasma.3α-Hydroxy Tibolone-13 CD3 was used as an internal standard (IS).The analyte and IS were extracted from human plasma by liquid-liquid extraction using ethyl acetate.Extracted samples were analyzed by UPLC-ESI-MS/MS.Chromatography was performed using binary gradient on UPLC analytical column.A linear calibration curve over the range of 0.100-35.000 ng/mL was obtained and lower limit of quantification (LLOQ) was 0.100 ng/mL demonstrating acceptable accuracy and precision.This method was successfully applied to a pharmacokinetic study in order to compare a test Tibolone 2.5 mg formulation vs.a reference 2.5 mg Tibolone tablet formulation in 50 post-menopausal/surgical menopause female human volunteers under fasting conditions.It is concluded that test formulation of Tibolone is bioequivalent to reference formulation of Tibolone.
A novel, fast, sensitive and robust method based on ultra-performance liquid chromatography coupled to atmospheric pressure electrospray ionization tandem mass spectrometry (UPLC-ESI-MS / MS) has been developed to separate two Tibolone stereoisomers ie, 3α-Hydroxy Tibolone and 3β Hydroxy Tibolone and to quantify 3α-Hydroxy Tibolone using p-toulenesulfonyl isocyanate (PTSI) as a derivatizing reagent in human plasma 3α-Hydroxy Tibolone-13 CD3 was used as an internal standard (IS). The analyte and IS were extracted from human plasma by liquid-liquid extraction using ethyl acetate. The extracted samples were analyzed by UPLC-ESI-MS / MS. Chromatography was performed using a binary gradient on UPLC analytical column. A linear calibration curve over the range of 0.100-35.000 ng / mL was obtained and lower limit of quantification (LLOQ) was 0.100 ng / mL demonstrating acceptable accuracy and precision. This method was successfully applied to a pharmacokinetic study in order to compare a test Tibolone 2.5 mg formulation vs. a reference 2.5 mg Tibolone tablet formulation in 50 post-menopausal / surgical menopause female human volunteers under fasting conditions. It is said that that test formulation of Tibolone is bioequivalent to reference formulation of Tibolone.