Determination of finasteride in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry with flow rate gradient.
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.
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ABSTRACT: A novel thermal gradient technique that combines flow and temperature programming has been developed for high-performance microbore liquid chromatography (muLC). Axial thermal gradient muLC (AxTG-muLC) modulates column temperature and changes analyte retention by introducing heated solvent into the column. The column, at ambient temperature, acts as a heat sink. Flow programming the mobile phase increases the rate of heat provided to the column and raises the average column temperature with time. For example, when introducing heated eluent at 100-degrees-C into a 1 mm x 5 cm reversed-phase column made of PEEK, the average column temperature is 40-degrees-C at 25 muL/min and 87-degrees-C at 400 muL/min. Thermal losses of the mobile phase down the length of the column were modeled with a two-dimensional distributed parameter model for a cylindrical packed bed. The change in average column temperature with flow rate was calculated and compared to chromatographic data. The AxTG-muLC technique maintains low column back pressure and peak resolution at high linear flow velocities. This results in good separation efficiency with reduced analysis time. Run-to-run cycle time is potentially reduced when compared to radially heating the column as the column is heated and cooled using the mobile phase.Analytical Chemistry 10/1993; 65(19). DOI:10.1021/ac00067a019 · 5.83 Impact Factor
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ABSTRACT: Finasteride inhibits type 25alpha-reductase activity, significantly reducing dihydrotestosterone levels. Consequent reductions in prostate volume, increases in urinary flow rates and improvements in symptoms compared with placebo have been observed in trials of up to 4 years' duration and in noncomparative extensions (for up to 6 years). Results from the 4-year placebo-controlled PLESS trial show finasteride to significantly reduce the risk of benign prostatic hypertrophy (BPH)-related acute urinary retention and the requirement for surgical intervention. Finasteride has significantly greater efficacy in patients with a large prostate (> or = 40 ml) than in patients with a small prostate. However, the predictive value of prostate size has been questioned. Results of an earlier comparative 1-year trial show terazosin monotherapy and terazosin plus finasteride therapy to be significantly more effective than both finasteride monotherapy and placebo in reducing symptom scores and improving maximum urinary flow rates. Prostatic volume was significantly reduced by finasteride monotherapy and combination therapy only. The overall efficacy of finasteride in patients with mild to moderate symptomatic BPH tended to be greater than that of serenoa repens (Permixon) in a 6-month trial. A US cost analysis model indicates that finasteride and terazosin are less expensive than transurethral resection of the prostate (TURP) during the first 2 years of initiation. Canadian cost-effectiveness and cost-utility analyses using decision analysis modelling have shown primary intervention with finasteride to provide more quality-adjusted life years (QALYs) at lesser cost than watchful waiting or TURP in patients with moderate symptoms who receive the drug for < or = 3 years and < or = 14 years, respectively, but fewer QALYs at a higher cost in patients with severe symptoms needing therapy for > or = 4 years. Confirmatory prospective economic studies are required. Finasteride appears to improve overall quality of life to a similar extent to serenoa repens; patient satisfaction appears similar with finasteride and TURP. Finasteride is generally well tolerated. Most commonly reported adverse effects are sexually related (1 to 2.1 %). Gynaecomastia has been reported in 0.4% of patients. CONCLUSIONS: Despite modest improvements in maximum urinary flow rates and symptom scores, finasteride is a first-line treatment option in those with moderate uncomplicated BPH, especially in patients with a large prostate (> or = 40 ml). It is also an option in patients with more severe symptoms who are unable or unwilling to undergo surgery and in those awaiting surgery. Importantly, finasteride appears to reduce disease progression, significantly decreasing the incidence of acute urinary retention and the requirement for surgical intervention; to date, no other pharmacological agent has been shown to reduce these outcomes.Drugs 04/1999; 57(4):557-81. · 4.13 Impact Factor
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ABSTRACT: A fully automated column-switching high-performance liquid chromatographic (HPLC) method was developed for the quantification of finasteride [N-(1,1-dimethylethyl)-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta- -carboxamide] in human plasma. Plasma samples were diluted with an equal volume of ethylene glycol-water (40:60, v/v), then the diluted sample (150 microliters) was injected into the HPLC system without clean-up. The analyte was retained on a pretreatment column, whereas plasma proteins and other endogenous components were washed out to waste. The analyte was transferred to the analytical column in the heart-cut mode and then detected at 210 nm. A quantification limit of 1 ng/ml was attained. There was a linear relationship between peak height and drug concentration in plasma in the range 1-50 ng/ml. This method was validated and applied to the assay of plasma samples to characterize pharmacokinetic parameters in clinical studies.Journal of chromatography. B, Biomedical applications 03/1996; 676(1):141-6. DOI:10.1016/0378-4347(95)00399-1