Produção Nacional
Revisado por pares
Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDA
2019; Hindawi Publishing Corporation; Volume: 2019; Linguagem: Inglês
10.1155/2019/7534609
ISSN2090-8865
AutoresRaquel Balestri Heleno Ferreira, Jonathaline Apollo Duarte, Flávio Dias Ferreira, Luís Flávio Souza de Oliveira, Michel Mansur Machado, Marcelo Donadel Malesuik, Fávero Reisdorfer Paula, Martin Steppe, Elfrides Eva Shermann Schapoval, Clésio Soldateli Paim,
Tópico(s)Inflammatory mediators and NSAID effects
ResumoA stability-indicating LC method was developed for quantification of linagliptin (LGT) and three synthetic impurities. The method utilizes a Thermo Scientific® RP-8 column (100 mm × 4.6 mm; 5 μm) with the PDA detector for quantitation of impurities. A mixture of 0.1% formic acid with pH 3.5 (A) and acetonitrile (B) was used as the mobile phase at a flow rate of 0.6 mL·min-1 with gradient elution. The percentage of mobile phase B increases from 30% to 70% over 5 min and decreases from 70% to 30% between 5 and 8 min. The method was validated according to International Council for Harmonization (ICH) guidelines. The LOD values obtained were 0.0171 μg·mL-1 and 0.015 μg·mL-1 for LGT and impurities, respectively. The LOQ values were 0.06 μg·mL-1 for LGT and impurities. In all cases, the correlation coefficients of LGT and impurities were >0.999, showing the linearity of the method. The % recovery of the LGT and added impurity were in the range of 92.92-99.79%. The precision of the method showed values less than 1.47% for LGT and less than 4.63% for impurities. The robustness was also demonstrated by small modifications in the chromatographic conditions. The selectivity was evidenced because the degradation products formed in stress conditions did not interfere in the determination of LGT and impurities. Toxicity prediction studies suggested toxicity potential of the impurities, which was confirmed using biological safety studies in vitro.
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