Rapid quantitative analysis of letrozole, fluoxetine and their metabolites in biological and environmental samples by MEKC

Abstract

A micellar electrokinetic chromatographic method has been developed to analyze biological (human serum, saliva and urine) and environmental samples (three different water samples) for letrozole (LE), fluoxetine and their main metabolites. For this purpose a 20 mM borate buffer (pH 9.5) containing 20 mM SDS and 12% v:v 2-propanol was used as the background electrolyte. The samples were hydrodynamically injected for 6 s, separated in a fused-silica capillary at 25 kV and 50 degrees C and detected at 230 nm. Under these conditions, the migration times for all the studied compounds ranged from 3.0 up to 8.0 min. Linearity ranges were determined as 125-1500 ng/mL, whereas detection limits were from 37 to 120 ng/mL in biological samples and a value of 6 ng/mL in water samples. According to the validation study, the developed method was proved to be accurate, precise, sensitive, specific, rugged and robust. This method was applied to the analysis of different biological fluids at clinical levels, including two urine samples from patients undergoing treatment with LE or fluoxetine, and also to environmental samples at potentially polluting level. Prior to the determination, the samples were purified and pre-concentrated by means of an extraction-preconcentration step with a C18 cartridge and by eluting the compounds with methanol.

Determination of letrozole, anastrozole and exemestane by capillary zone electrophoresis

“…At the beginning of determinations we have selected the type of background electrolyte (BGE) by checking the electrophoretic behavior of the analytes using an acidic BGE -phosphoric acid 25 mM and a basic BGE -25 mM borax. After our prelimary results we selected a 25 mM borax (pH 9.3) as BGE also taking in consideration previous electrophoretic studies [17][18][19][20][21].…”

“…Several capillary electrophoretic methods have been reported for determination of AIs in combination with other compounds, mainly micellar electrokinetic capillary chromatographic (MEKC) [17][18][19][20]. So far, there is no published electrophoretic method for the simultaneous determination of all three AIs selected in this research.…”

Letrozole Determination by Capillary Zone Electrophoresis and UV Spectrophotometry Methods

“…Initially, we choose to start with a 25 mM phosphate buffer, an acidic background electrolyte (BGE), but the electrophoretic signal of the substance was difficult to detect (low value of area and height). A standard BGE containing 25 mM borax (pH 9.3) was than selected, taking in consideration also previous electrophoretic studies, however the disadvantage in a basic environment was that LET migrated very close to the electroosmotic flow (EOF) [16][17][18][19]. Adding sodium dodecyl sulfate (SDS) in the 25 mM borax BGE did not resolved the problem.…”

“…Until now, on a base of detailed literature survey, it was found that LET could be estimated along with other compounds only by MEKC [16][17][18][19].…”

“…Similar data has been previously obtained at the administation of a single dose of letrozole (2.5 mg) with 14C-labeled within two weeks when the recovered radioactivity from urine was 88.2 ± 7.6% (5.0 ± 2.4% unmetabolized letrozole, 63.2 ± 11.2% carbinole glucuronide and about 8% other metabolites) [15]. A few capillary electrophoretic (CE) methods for LET determination have been already reported in the literature, mainly micellar electrokinetic capillary chromatographic (MEKC) [16][17][18][19]. The electrophoretic methods are more advantageous through accessibility than other expensive analytical methods as HPLC and RP-HPLC, LC-MS/MS or SPE-UPLC-MS/MS [20][21][22][23][24].…”