Simultaneous Determination of Residual Formic Acid and Content of Sulfate in Clopidogrel Bisulfate by Ion Chromatography

A method for the simultaneous determination of residual formic acid and the content of sulfate (SO₄²⁻) in clopidogrel bisulfate active pharmaceutical ingredient (API) by ion chromatography (IC) was developed. Clopidogrel bisulfate API was sonicated by 2 mmol/L NaOH aqueous solution and then filtered. The analysis was performed on a Dionex IonPac AS11-HC analytical column (4 mm×250 mm) in combination with a Dionex IonPac AG11-HC guard column (4 mm×50 mm). The eluent was KOH produced on-line with an EG 500 KOH in the gradient mode at a flow rate of 1.3 mL/min. The column temperature was kept at 30 ℃ and the injection volume was 25 μL. The suppressor current was 90 mA. The test results showed that good linearity existed over the range of 0.020 0~1.00 mg/L for formic acid, and 10.0~40.0 mg/L for sulfate, respectively. The detection limits (LODs) of formic acid and sulfate were 10.0, 50.0 μg/L, respectively, and the quantification limits (LOQs) were 20.0, 100 μg/L, respectively. The method is simple, highly sensitive, and reproducible, and could be suitable for the detection of residual formic acid and the content of sulfate in clopidogrel bisulfate API.