Article

A rapid, simple, specific liquid chromatographic-electrospray mass spectrometry method for the determination of finasteride in human plasma and its application to pharmacokinetic study.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, PR China.
Journal of Pharmaceutical and Biomedical Analysis (Impact Factor: 2.95). 04/2007; 43(4):1507-13. DOI: 10.1016/j.jpba.2006.10.024
Source: PubMed

ABSTRACT A fast, accurate, sensitive, selective and reliable method using reversed-phase high-performance liquid chromatography-mass spectrometry coupling with an electrospray ionization interface was developed and validated for the determination of finasteride in human plasma. After deprotienation with acetonitrile, centrifugation, evaporation to dryness and dissolving in mobile phase, satisfactory separation was achieved on a Hypersil-Keystone C(18) reversed-phase column using a mobile phase consisting of acetonitrile-water (46:54, v/v), 0.1% acetic acid and 0.1% trifluoracetic acid. Carbamazepine (IS) was used as internal standard. This method involved the use of the [M+H](+) ions of finasteride and IS at m/z 373 and 237 with the selective ion monitoring (SIM) mode. The calibration curve was linear in the range of 0.2-120 ng ml(-1). The limit of quantification for finasteride in plasma was 0.2 ng ml(-1) with good accuracy and precision. The intra-assay precision and accuracy were in the range of 2.1-11.2% and -1.3% to 8.5%, respectively. The inter-assay precision and accuracy were in the order of 3.4-12.1% and -1.5% to 11.5%, respectively. The mean sample extract recoveries of the method were higher than 85% and 74% for finasteride and internal standard (IS), respectively. The assay has been successfully used to estimate the pharmacokinetics of finasteride after oral administration of a 5mg tablet of finasteride to 24 healthy volunteers.

1 Bookmark
 · 
38 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, an attempt was made to describe and validate liquid chromatography-electrospray ionization tandem mass spectrometry as a fast, sensitive and reproducible method for determining finasteride in human plasma. Finasteride and internal standard (pantoprazole) were extracted by liquid-liquid extraction using methyl tert-butyl ether. Separation was performed by using a flow rate gradient on a reverse phase C18 column at 25°C. The mobile phase consisted of methanol-water (70:30, v/v) containing 0.5% anhydrous formic acid. The protonated analytes were quantitated in positive ionization by multiple reaction monitoring in mass spectrometry. The mass transitions are m/z 373.4→305.3 and 384.1→200.0 for finasteride and pantoprazole, respectively. The method had a run time of 3.6 min and a linear calibration curve at a range of 0.2-100 ng mL(-1) (r2=0.9958). The lower limit of quantification was 0.2 ng mL(-1). The extraction recoveries of finasteride from the biological matrix were more than 82.7%, and the intra- and inter-day precision of the assay at four concentrations were 2.4-8.0% with an accuracy of 94.3-105.8%. The developed method requires less plasma (0.1 mL), but has high sensitivity. The validated method has been successfully used to analyze human plasma samples in pharmacokinetic or bioequivalence studies.
    European Journal of Drug Metabolism and Pharmacokinetics 01/2011; 35(3-4):137-46. · 1.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A stability-indicating micellar electrokinetic chromatography method has been developed and validated for determination of finasteride. Analysis was performed by using 50 cm × 100 µm i.d. (effective length 42.8 cm) fused silica capillary and background electrolyte of 50 mM NaH2PO4 (pH 3) buffer containing 10 mM sodium dodecyl sulfate as surfactant. Applied potential was selected as − 15 kV at 25°C and the detection was at 210 nm. The calibration curve was linear in the range of 5-50 µg.mL. Effects of pH, capillary temperature, applied voltage and buffer concentration were investigated. Degradation studies were carried out under acidic (1.0 M HCl), basic (1.0 M NaOH), oxidative (%10 H2O2), thermal (60°C) and UV-light (254 nm) conditions and it was found that finasteride was degraded under acidic, basic and oxidative stress conditions. The method was successfully applied to the determination of finasteride in tablet formulations.
    Journal of Liquid Chromatography &amp Related Technologies 02/2013; 36(6):781-791. · 0.57 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A fast, accurate, sensitive, selective and reliable method using reversed-phase high performance liquid chromatography coupled to electrospray ionization ion trap mass spectrometry was developed and validated for the determination of finasteride in human plasma. After protein precipitation with perchloric acid, satisfactory separation was achieved on a Zorbax Eclipse® C8 analytical column using a mobile phase consisted of acetonitrile, 2 mM ammonium formate buffer (58:42, pH adjusted at 2.5 using formic acid); the flow rate was 0.25 mLmin-1 and the column oven was set to 50°C. Tamoxifen citrate was used as internal standard. This method involved the use of [M + H]+ ions of finasteride and IS at m/z 373 and 372 respectively with the selected ion monitoring (SIM) mode. The calibration curve was linear over the range of 0.1–60 ng mL−1. The limit of quantification for finasteride in plasma was 0.1 ng mL−1. The intra-day and inter-day repeatability (precision) were 2.68-13.87% and 2.14-14.69% respectively. Intra-day and inter-day accuracy were 98-101.57% and 99.7-110%. The assay method has been successfully used to estimate the pharmacokinetics of finasteride after oral administration of a 5 mg tablet of finasteride in 12 healthy volunteers.
    Iranian journal of pharmaceutical research (IJPR) 01/2012; 11(7):59-67. · 0.54 Impact Factor