Sensitive and rapid high-performance liquid chromatography tandem mass spectrometry method for estimation of fulvestrant in rabbit plasma.

A rapid and sensitive high-performance liquid chromatography and electrospray tandem mass spectrometry method was developed and validated for estimation of fulvestrant in rabbit plasma using liquid-liquid extraction. The separation and quantification of fulvestrant were achieved by reverse-phase chromatography on a Sunfire C18 column (50 x 2.1. i.d., 3.5 microm) with isocratic elution at a flow rate of 300 microL/min using norethistrone as an internal standard from 500 microL plasma sample. The method was validated over the concentration range from 0.092 to 16.937 ng/mL with a lower limit of detection of 0.023 ng/mL. The intra-day and inter-day accuracy and precision were within 10%. The recovery was 85 and 90% for fulvestrant and norethistrone respectively. The chromatographic run time was only 2.5 min.

Matrix-type transdermal drug delivery system of trandolapril: in vitro and ex vivo characterization.

The purpose of the investigation was to develop and evaluate matrix-type transdermal drug delivery systems (TDDSs) of trandolapril. Matrix-type TDDSs of trandolapril were prepared by solvent evaporation technique. Eight formulations (composed of Eudragit RL 100 and Hydroxypropyl methyl cellulose 15 cps at a ratios of 2:8, 4:6, 6:4, 8:2 in formulations A1, A2, A3, A4; and Eudragit RS 100 and Hydroxypropyl methyl cellulose 15 cps in the same ratios in formulations B1, B2, B3, B4, respectively) were prepared. All formulations contained 5% w/w menthol as penetration enhancer and 15% w/w propylene glycol as plasticizer in ethanol as solvent. The prepared TDDSs were evaluated for physicochemical characteristics, in vitro release and ex vivo permeation. The physicochemical interactions between trandolapril and polymers were investigated by Fourier transform infrared spectroscopy. The results suggested that there is no physicochemical interaction between drug and polymers. The maximum drug release in 24 h for A series formulations was 95.45% (A1), 95.82% (A2), and it was 95.26% (B1), 95.69% (B2) for B series formulations, which are significantly (P < 0.05) different than the lowest values 78.79% (A3), 66.9% (A4) and 82.64% (B3), 71.67% (B4). The formulations A1 (flux 25.03 ± 0.98 µg/cm(2)/h) and B1 (flux 24.62 ± 0.63 µg/cm(2)/h) showed maximum skin permeation in the respective series. The flux obtained with formulations A1 and B1 meets the required flux (37.04 µg/h/cm(2)) with a minimum patch area (3.9 cm(2)). Matrix-type transdermal therapeutic systems of trandolapril could be prepared with the required flux using menthol as penetration enhancer.