Determination of residual amines used in bulk drug synthesis by pre-column derivatization with 3,5-dinitrobenzoyl chloride and high-performance liquid chromatography
1997; Elsevier BV; Volume: 766; Issue: 1-2 Linguagem: Inglês
10.1016/s0021-9673(96)01058-8
ISSN1873-3778
AutoresJames A. Morley, Lee Elrod, Cathie L. Linton, Dean I. Shaffer, Suzanne Krogh,
Tópico(s)Analytical Methods in Pharmaceuticals
ResumoA rapid, simple and general method for determining residual amines used in bulk drug manufacturing is described. The method uses a modified Schotten–Baumann reaction to prepare the 3,5-dinitrobenzoyl derivatives of primary and secondary amines. Unlike previously reported procedures, the method does not require the isolation of the derivative and the reaction solution is chromatographed directly without further sample treatment. Application of the method to the determination of residual piperazine in 2-methylpiperazine (I), of 3-aminopyrrolidine in 3-(tert-butoxycarbonylamino)pyrrolidine (II) and N-(2-tetrahydrofuroyl)piperazine in 2-([4-(tetrahydro-2-furanyl)carbonyl]-1-piperazinyl)-6,7-dimethoxy-4-quinazolinamine, monohydrochloride, dihydrate (III) is described. Linearity was demonstrated with correlation coefficients ≥0.9999 for all examples. Assay precision (R.S.D. values) ranged from ±2.9% for the determination of 2.6% 3-aminopyrrolidine in (II) to ±11% for the determination of 0.21% N-(2-tetrahydrofuroyl)piperazine in (III). The accuracy of the determination ranged from 100.7 to 103.8%. The procedure is also used to determine the chiral purity of (3S)-(−)-(tert-butoxycarbonylamino)pyrrolidine.
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