Residual solvent determination by head space gas chromatography with flame ionization detector in omeprazole API

Abstract

Residual solvents in pharmaceutical samples are monitored using gas chromatography with head space. Based on good manufacturing practices, measuring residual solvents is mandatory for the release testing of all active pharmaceutical ingredients (API). The analysis of residual organic solvents (methanol, acetone, cyclohexane, dichloromethane, toluene) in Omeprazole, an active pharmaceutical ingredient was investigated. Omeprazole is a potent reversible inhibitor of the gastric proton pump H+/K+-ATPase. The Head space gas chromatography (HSGC) method described in this investigation utilized a SPB TM -624, Supelco, 30 m long x 0.25 mm internal diameter, 1.4µm-thick column. Since Omeprazole is a thermally labile compound, the selection of the proper injector temperature is critical to the success of the analysis. The injector temperature was set at 170°C to prevent degradation. The initial oven temperature was set at 40°C for 12 min and programmed at a rate of 10°C min −1 to a final temperature of 220°C for 5 min. Nitrogen was used as a carrier gas. The sample solvent selected was N,N-dimethylacetamide. The method was validated to be specific, linear, precise, sensitive, rugged and showed excellent recovery.Uniterms: Headspace-gas chromatography. Omeprazole. Method validation. Residual solvents release testing.Solventes residuais em amostras farmacêuticas são monitoradas utilizando-se cromatografia a gás "headspace". Com base nas boas práticas de fabricação, a medida de solventes residuais é obrigatória para o teste de liberação de todos os ingredientes farmacêuticos (API). Efetuou-se a análise de solventes orgânicos residuais (metanol, acetona, cicloexano, diclorometano, tolueno) em omeprazol, ingrediente farmacêutico ativo. O omeprazol é potente inibidor reversível da bomba de prótons H+/K+-ATPase. A cromatografia a gás "headspace" (HSGC) descrita nessa pesquisa utilizou um SPB TM -624, Supelco, de 30 m de comprimento x 0,25 mm de diâmetro interno, e coluna de 1,4 µm de espessura. Considerandose que o omeprazol é termicamente lábil, a seleção da temperatura apropriada do injetor é crítica para impedir a degradação. A temperatura inicial do forno foi de 40 °C, por 12 minutos, e programada à taxa de acréscimo de 10 °C min −1 até a temperatura final de 220 °C, por 5 minutos. Nitrogênio foi utilizado como gás de transporte. Selecionou-se como solvente a N,N-dimetilacetamida. O método foi validado mostrando-se específico, linear, preciso, sensível, robusto e com excelente recuperação.Unitermos: Cromatografia a gás "headspace". Omeprazol. Método de validação. Teste de liberação de solventes residuais.

Analysis of residual crosslinking agent content in UV cross-linked poly(ethylene oxide) hydrogels for dermatological application by gas chromatography

“…Three levels of PETRA concentrations were measured in triplicate for each set of variation. The acceptance criteria were set as RSD values not exceeding 10% for each concentration level and a maximum cumulative (overall) RSD of 15% [36] . The obtained results are summarized in Table 5 .…”

Determination of volatiles in pharmaceutical certified reference materials

“…One of the reasons for that may be the previously reported difficulty to completely remove polar residual solvents from sample solutions for sHS-GC analysis. 33,36 Chen et al, 38 for instance, studied the recoveries of 44 residual solvents in pharmaceuticals and reported values as low as 57% for acetone at 2-90 ppm levels. Another possible reason why the volatile mass fraction did not match the difference LOD -KF may be related to solvent-solute effects, 47 which means interactions between APIs and residual solvents in solution.…”

“…For less polar or apolar samples, high boiling point solvents such as N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO) 2,34 and N,N-dimethylacetamide (DMA) 36 may be used. Since organic diluents seriously reduce the method sensitivity, 2 water is usually added to the organic phase to reduce K and increase C g .…”

Headspace gas chromatographic analysis of residual solvents in pharmaceuticals: comparison of two matrix media

“…The nature of the matrix medium is of primary importance as has an essential influence on the amount of the analytes in the headspace and thus on the determination sensitivity. For residual solvents determination in pharmaceuticals, water [8], dimethylsulfoxide [9,15], N,N-dimethylacetamide [16], N,N-dimethylformamide (DMF) [15], benzyl alcohol [17], liquid paraffin [18] and ionic liquids [3,11] were suggested as matrix media. Recently, for residual solvents determination deep eutectic solvents (DESs) have been proposed [7,8,19].…”