Stability‐Indicating HPLC Method for Captopril Through Pre‐Column Derivatization with Pd(II)

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Abstract
An accurate, sensitive, and specific reversed phase high performance liquid chromatographic (HPLC) method was developed for the determination of captopril (CPT). The proposed method depends on the complexation ability of CPT with Pd(II) using a pre‐column derivatization technique. Reversed phase chromatography was conducted using a Luna 5 µ phenyl‐hexyl [250×4.6 mm i.d.] stainless steel column at ambient temperature with specific photometric‐detection at 380 nm. A solution containing 0.025% w/v of Pd(II) chloride in a mixture of acetonitrile‐methanol‐water containing 10 mM Britton‐Robinson buffer [BRb] of pH 4.0 and 0.25 M KCl solution [1∶4∶5 v/v/v] was used as a mobile phase,which was pumped at a flow rate of 0.75 mL min−1. The method showed excellent linearity in the range 2–32 µg · mL−1 with a limit of detection [S/N=2] of 0.18 µg · mL−1 [8.28×10−7 M]. The suggested method was successfully applied for the analysis of CPT in bulk, single and combined dosage forms with average % recoveries of 99.66±0.70, 99.63±0.68, and 99.32±0.77, respectively. Hydrochlorothiazide, which is frequently co‐formulated with CPT, did not interfere. The proposed method could be used successfully for the determination of CPT in the presence of its disulphide dimer in pure form and in pharmaceutical preparations. This finding proved the stability‐indicating character of the method. The results obtained were favorably compared to those obtained by the official method.

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