CATION-EXCHANGE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY OF PIPERAZINE IN SOME PHARMACEUTICAL FORMULATIONS

An assay method for the quality control of piperazine in some formulat ions was developed utilizing cation-exchange high-performance liquid c hromatography. A sample solution, containing 1-phenylpropanolamine-HCl as internal standard, was chromatographed on a 250 x 4.6 mm I.D. Ultr asil CX column with an aqueous mobile phase containing 0.07 M KH2PO4 ( pH 3.0)-triethylamine (100:0.01), and differential refractive index de tection. Piperazine and 1-phenylpropanolamine-HCl eluted at about 4.9 and 6.4 min, respectively, with a resolution of 2.1. Piperazine/intern al standard peak area ratio was linear over 4-477 mu g of piperazine d ihydrochloride monohydrate injected (r = 0.9994). The limit of quantit ation was 5.3 mu g of piperazine dihydrochloride monohydrate injected. Recovery studies covering a range of +/- 33% of label amount of piper azine 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 com mercial formulations were higher than those obtained by the USP method . Stability tests indicated that degradation products of piperazine, f ormed upon hydrogen peroxide treatment, did not interfere with the pip erazine peak, whereas piperazine dihydrochloride aqueous solutions wer e fairly stable in acid, base, and exposure to short-wavelength UV lig ht.