Development and validation of a general derivatization HPLC method for the trace analysis of acyl chlorides in lipophilic drug substances.
J Pharm Biomed Anal
; 140: 327-333, 2017 Jun 05.
Article
em En
| MEDLINE
| ID: mdl-28391005
ABSTRACT
Acyl chlorides are important acylating agents in the synthesis of active pharmaceutical ingredients. Determining the residual acyl chlorides in drug substances is a challenge due to their high reactivity and the matrix interferences from drug substances and their related impurities. This paper describes a general derivatization HPLC method for the determination of aromatic and aliphatic acyl chlorides in lipophilic drug substances. Since most drug substances have weak absorptions in the visible range (above 380nm), the nitro-substituted anilines and nitro-substituted phenylhydrazines were selected as the derivatization reagents due to their weak basicity and red-shift of UV absorption spectra. The maximum wavelength and absorption intensity of nitro-substituted anilines decreased after derivatization with acyl chlorides, whereas the derivatization products of nitro-substituted phenylhydrazines showed the slight increases of maximum wavelength and absorbance intensity. Hence, 2-nitrophenylhydrazine was selected as the suitable derivatization reagent because the derivatives have the maximum UV wavelength absorbance at 395nm, which could largely minimize the matrix interferences. The optimization of the concentration of 2-nitrophenylhydrazine is important for the sensitivity and stability of derivatives. Other reaction conditions including reaction temperature, time and the influence of three competitive solvents (water, methanol and ethanol) on the reaction efficiency were also studied. After derivatization with 100µgmL-1 2-nitrophenylhydrazine at room temperature for 30min, the method was validated for high specificity and sensitivity with the detection limits in the range of 0.01-0.03µgmL-1. The proposed method was applied as a generic method to determine the residual acyl chlorides in lipophilic drug substances.
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MEDLINE
Assunto principal:
Cromatografia Líquida de Alta Pressão
Idioma:
En
Revista:
J Pharm Biomed Anal
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China