Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDA
A 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...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Analytical Methods in Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2019/7534609 |
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| author | Raquel Balestri Heleno Ferreira Jonathaline Apollo Duarte Flávio Dias Ferreira Luis Flávio Souza de Oliveira Michel Mansur Machado Marcelo Donadel Malesuik Fávero Reisdorfer Paula Martin Steppe Elfrides Eva Shermann Schapoval Clésio Soldateli Paim |
| author_facet | Raquel Balestri Heleno Ferreira Jonathaline Apollo Duarte Flávio Dias Ferreira Luis Flávio Souza de Oliveira Michel Mansur Machado Marcelo Donadel Malesuik Fávero Reisdorfer Paula Martin Steppe Elfrides Eva Shermann Schapoval Clésio Soldateli Paim |
| author_sort | Raquel Balestri Heleno Ferreira |
| collection | DOAJ |
| description | A 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. |
| format | Article |
| id | doaj-art-7527b612ee464a78a8c3262f0a6b5f54 |
| institution | Kabale University |
| issn | 2090-8865 2090-8873 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Analytical Methods in Chemistry |
| spelling | doaj-art-7527b612ee464a78a8c3262f0a6b5f542025-02-03T01:26:33ZengWileyJournal of Analytical Methods in Chemistry2090-88652090-88732019-01-01201910.1155/2019/75346097534609Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDARaquel Balestri Heleno Ferreira0Jonathaline Apollo Duarte1Flávio Dias Ferreira2Luis Flávio Souza de Oliveira3Michel Mansur Machado4Marcelo Donadel Malesuik5Fávero Reisdorfer Paula6Martin Steppe7Elfrides Eva Shermann Schapoval8Clésio Soldateli Paim9Laboratório de Pesquisa em Desenvolvimento e Controle de Qualidade, Universidade Federal do Pampa, Uruguaiana, RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Pampa, Uruguaiana, RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Pampa, Uruguaiana, RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Pampa, Uruguaiana, RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Pampa, Uruguaiana, RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Pampa, Uruguaiana, RS, BrazilLaboratório de Pesquisa em Desenvolvimento e Controle de Qualidade, Universidade Federal do Pampa, Uruguaiana, RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, BrazilPrograma de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, BrazilLaboratório de Pesquisa em Desenvolvimento e Controle de Qualidade, Universidade Federal do Pampa, Uruguaiana, RS, BrazilA 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.http://dx.doi.org/10.1155/2019/7534609 |
| spellingShingle | Raquel Balestri Heleno Ferreira Jonathaline Apollo Duarte Flávio Dias Ferreira Luis Flávio Souza de Oliveira Michel Mansur Machado Marcelo Donadel Malesuik Fávero Reisdorfer Paula Martin Steppe Elfrides Eva Shermann Schapoval Clésio Soldateli Paim Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDA Journal of Analytical Methods in Chemistry |
| title | Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDA |
| title_full | Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDA |
| title_fullStr | Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDA |
| title_full_unstemmed | Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDA |
| title_short | Biological Safety Studies and Simultaneous Determination of Linagliptin and Synthetic Impurities by LC-PDA |
| title_sort | biological safety studies and simultaneous determination of linagliptin and synthetic impurities by lc pda |
| url | http://dx.doi.org/10.1155/2019/7534609 |
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