Method development and validation for trifluoroacetic acid determination by capillary electrophoresis in combination with capacitively coupled contactless conductivity detection (CE-C4D)

Abstract

A method was developed to determine traces of trifluoroacetic acid as impurity in synthetic or semi-synthetic drugs as antibiotics, macropeptides, etc. Capillary electrophoresis in combination with capacitively coupled contactless conductivity detection (CE-C(4)D) was used due to lack of UV absorbance property of trifluoroacetic acid (TFA). The optimized method took less than 1 min with good linearity (R(2)=0.9995) for trifluoroacetic acid concentration from 2 to 100 ppm. It also has a good repeatability expressed by the relative standard deviation (% RSD) which is 1.2 and 2.1% for intraday and interday precision, respectively, at 50 ppm TFA, and good sensitivity with 0.34 ppm, 1.2 ppm LOD and LOQ, respectively. In addition, the content of TFA in synthetic drug, was determined using the validated method which gave good linearity (R(2)=0.9996) for trifluoroacetic acid spiked into drug in a concentration range of 2-80 ppm, with good intraday repeatability of 2.0%. The analysis is performed in a background electrolyte composed of 20mM morpholinoethane-sulfonic acid (Mes) and 20mM L-histidine (L-His) pH 6.1. Cetyltrimethylammonium bromide (CTAB) was added as flow modifier in a concentration (0.2mM) lower than the critical micellar concentration. Ammonium formate 6 ppm was used as internal standard. The applied voltage was 30 kV in reverse polarity. A fused silica capillary with 75 μm internal diameter and total length 47 cm (31 cm to C(4)D detector and 37 cm to DAD detector) was used.