Cation-exchange high-performance liquid chromatographic assay of piperazine in some pharmaceutical formulations

• Published in: Journal of Chromatography A 1995-02, Vol.693 (2), p.307-314
• Main Authors: Tan, Henry S.I., Jianling Xu, Yaohan Zheng
• Format: Article
• Language: English
• ISSN: 0021-9673
• DOI: 10.1016/0021-9673(94)01040-L

An assay method for the quality control of piperazine in some formulations was developed utilizing cation-exchange high-performance liquid chromatography. A sample solution, containing 1-phenylpropanolamine-HCl as internal standard, was chromatographed on a 250 × 4.6 mm I.D. Ultrasil CX column with an aqueous mobile phase containing 0.07 M KH 2PO 4 (pH 3.0)-triethylamine (100:0.01), and differential refractive index detection. Piperazine and 1-phenylpropanolamine-HCl eluted at about 4.9 and 6.4 min, respectively, with a resolution of 2.1. Piperazine/internal standard peak area ratio was linear over 4–477 μg of piperazine dihydrochloride monohydrate injected ( r = 0.9994). The limit of quantitation was 5.3 μg of piperazine dihydrochloride monohydrate injected. Recovery studies covering a range of ± 33% of label amount of piperazine in commercial formulations gave an overall recovery (± S.D., n = 6) of 100.2 ± 0.8% from spiked tablet placebos, and 100.3 ± 1.0% from spiked syrup placebos. The method was tested to be rugged based on Youden and Steiner's experimental design. The assay results of commercial formulations were higher than those obtained by the USP method. Stability tests indicated that degradation products of piperazine, formed upon hydrogen peroxide treatment, did not interfere with the piperazine peak, whereas piperazine dihydrochloride aqueous solutions were fairly stable in acid, base, and exposure to short-wavelength UV light.