Validation of a generic analytical procedure for determination of residual solvents in drug substances

Klick, Silke; Sköld, Agneta

doi:10.1016/j.jpba.2004.06.014

Cited by 53 publications

(35 citation statements)

References 7 publications

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“…A fraction of the headspace vapor is sampled and introduced into a GC system. Injection of the analytes evaporated from the sample into the GC system could minimize the contamination of the GC instrument and deterioration of the GC capillary column [3][4][5][6][7][8][9]. A comprehensive analytical procedure using HS-GC for residual solvents in drug substances and drug products is described in the United States Pharmacopeia 37 (USP 37) [10].…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of an Analytical Method for Simultaneous Quantitation of Organic Volatile Impurities in Technical-Grade Active Ingredients of Pesticides and Agrochemicals by Headspace Gas Chromatography

et al. 2015

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A simple, rapid, accurate, precise headspace gas chromatographic (HS-GC) method was developed and validated for simultaneous quantitation of organic volatile impurities (residual solvents) in technical-grade active ingredients (TGAIs) of pesticides and agrochemicals. The HS-GC method utilizes conventional capillary columns. The HS-GC operating conditions were optimized, and 18 organic volatile impurities were efficiently separated. The versatility of the method was confirmed in terms of validation characteristics of specificity, limit of quantitation, linearity, accuracy, and precision. The proposed method was successfully applied to the analysis of pesticide and agrochemical TGAIs.

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Section: Introductionmentioning

confidence: 99%

Development and Validation of an Analytical Method for Simultaneous Quantitation of Organic Volatile Impurities in Technical-Grade Active Ingredients of Pesticides and Agrochemicals by Headspace Gas Chromatography

et al. 2015

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“…These polar organic solvents have a higher boiling point than water and a high capacity for dissolving a wide range of organic substances. The HSGC method using DMF as the sample diluent has a higher precision than when water is used in the quantification of residual solvents in drug substances [12]. In the JECFA specification of bixin-based products, DMF is designated as the solvent to dissolve and dilute samples in high-performance liquid chromatography (HPLC) analysis for impurities [9].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Residual Solvents in Annatto Extracts Using a Static Headspace Gas Chromatography Method

Itô¹,

Ishizuki²,

Sekiguchi³

et al. 2012

AJAC

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An analytical method for the quantification of residual solvents in annatto extracts, natural food colorants, was established using a static headspace gas chromatography (HSGC) coupled with a flame ionization detector (FID). As a sample diluent in a headspace sampling, dimethylformamide (DMF) was selected owing to its high capacity for dissolving both bixin-based and norbixin-based annatto extracts. The quantification of residual solvents was performed using the external standard method. The linearity of the calibration curves was assured with relative coefficients (R 2 ) that were greater than 0.999. The recoveries of all standard solvents spiked in the annatto extracts were in the range from 95.1% to 107.1% to verify the accuracy and the relative standard deviation (RSD%) values (n = 3) were in the range from 0.57% to 3.31%. The quantification limits (QL) were sufficiently lower than the limits specified by Joint FAO/WHO Expert Committee on Food Additives (JECFA). With the established HSGC method, six residual solvents (methanol, ethanol, 2-propanol, acetone, ethyl acetate, and hexane) in 23 commercial annatto-extract products that consist of seven bixin-based and 16 norbixin-based products were quantified. The levels of residual ethyl acetate and hexane in all products were lower than the specified limits of JECFA. However, three samples of bixin-based products showed higher levels of residual 2-propanol (approximately 313.9 -427.7 ppm) than the specified limit. Other bixin products also showed higher concentrations of residual methanol (approximately 166.6 -394.7 ppm) and residual acetone (approximately 75.2 -179.8 ppm) than the limits of JECFA. In the case of norbixin-based products, nine samples showed higher levels of residual acetone (approximately 42.6 -139.5 ppm) than the limits of JECFA. This is the first survey of residual solvents in annatto extracts using the validated HSGC method.

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“…Residual solvent specification limits, set in accordance with the toxicity of solvents, vary from a few ppm to thousands of ppm. HSGC determination of residual solvents is nowadays a mature technique (Grodowska et al, 2010;Puranik et al, 2009;Groman et al, 2008;Alzaga, 2007;Camarasu, 2006;Michulec et al 2005;Rocheleau et al, 2004;Klick, 2004;Snow, 2002;Hymer et al, 2003;Iofer et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

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

Pandey¹,

Pandey²,

Kumar³

et al. 2011

Braz. J. Pharm. Sci.

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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.

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Validation of a generic analytical procedure for determination of residual solvents in drug substances

Cited by 53 publications

References 7 publications

Development and Validation of an Analytical Method for Simultaneous Quantitation of Organic Volatile Impurities in Technical-Grade Active Ingredients of Pesticides and Agrochemicals by Headspace Gas Chromatography

Development and Validation of an Analytical Method for Simultaneous Quantitation of Organic Volatile Impurities in Technical-Grade Active Ingredients of Pesticides and Agrochemicals by Headspace Gas Chromatography

Analysis of Residual Solvents in Annatto Extracts Using a Static Headspace Gas Chromatography Method

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

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