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2 Acta Chromatographica

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Evaluation of the pharmacokinetics of the simultaneous quantification of letrozole and palbociclib in rat plasma by a developed and validated HPLC–PDA

100%

Al-Shehri M. , Hefnawy M. , Abuelizz H. , Alzamil A.

2020

tom Vol. 32, no. 3

170--178

The US Food and Drug Administration (FDA) has affirmed the use of letrozole (LTZ combined with palbociclib (PLB) to treat breast malignant tumor growth in postmenopausal women. A straightforward and extremely sensitive reversed-phase high-performance liquid chromatography method with photodiode array detection (RP-HPLC–PDA) was created and validated for the simultaneous determination of LTZ and PLB in rat plasma. The parameters used to give the best separation were a C18 column (150 mm × 4.6 mm, 3.5 μm) as the stationary phase with an isocratic mobile phase composed of methanol–30 mM ammonium acetate at a ratio of 60:40 (v/v), pH = 5.5, a flow rate of 0.8 mL/min, and detection wavelengths of 240 and 220 nm for LTZ and PLB, respectively. The developed method was assessed by the FDA rules over a range of 10–600 ng/mL for LTZ and PLB. The mean of %recovery of LTZ and PLB extracted from rat plasma by acetonitrile-based deproteinization was 91.06 ± 2.73 and 90.30 ± 1.95%, respectively, and the limits of detection were 5 ng/mL for LTZ and 7 ng/mL for PLB in rat plasma. The mean values of Tmax and Cmax were 6 ± 0.00 h and 266.96 ± 21.23 ng/mL for LTZ and 4 ± 0.00 h and 508.75 ± 61.56 ng/mL for PBL, respectively, after intraperitoneal administration of both drugs to rats. The developed HPLC–PDA method was demonstrated to be robust and was effectively applied to study the pharmacokinetics of LTZ and PLB in rat plasma.

Simple HPLC method for simultaneous quantification of nicotine and cotinine levels in rat plasma after exposure to two different tobacco products

86%

Alhusban A. A. , Hammad A. M. , Alzaghari L. F.

tom Vol. 35, no. 1

106--114

Purpose: Development and validation of a selective analytical method to accurately and precisely quantify nicotine and cotinine levels in rat's plasma after exposure to tobacco cigarettes and tobacco water-pipe. Methods: An easy HPLC-Photodiode-Array Detection (PDA) method was developed and validated for simultaneous determination of nicotine and cotinine levels in plasma of 15 rats (10 rats after tobacco products exposure and 5 control rats). Nicotine and cotinine were extracted in one step from plasma using acetonitrile and concentrated to lowest volume using nitrogen stream. Results: The developed method offered a rapid analysis time of 14 min with single step of analytes extraction from rat's plasma with recovery percentage range between 93 and 95% and excellent linearity with correlation factor more than 0.994 with analytical range between 50 and 1000 ng mL⁻¹ and LOD of 25 ng mL⁻¹ and 23 ng mL⁻¹ for nicotine and cotinine, respectively. The analysis of rat's plasma after 28 days of exposure to tobacco cigarettes and tobacco water-pipe revealed that the average concentrations of 376 ng mL⁻¹ for cotinine and 223 ng mL⁻¹ for nicotine were obtained after tobacco cigarettes exposure, and 220 ng mL⁻¹ for cotinine and 192 ng mL⁻¹ for nicotine after tobacco water-pipe exposure. Conclusion: Higher nicotine and cotinine levels were found in plasma after tobacco cigarettes exposure than water-pipe exposure which may have potential undesirable effects on passive smokers in both cases.