Static headspace gas chromatography of (semi-)volatile drugs in pharmaceuticals for topical use

Yarramraju, Sitaramaraju; Hul, Ariane van; Wolfs, Kris; Schepdael, Ann Van; Hoogmartens, Jos; Adams, Erwin

doi:10.1016/j.jpba.2008.04.006

Cited by 24 publications

(15 citation statements)

References 22 publications

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Section: Static Headspace Gas-chromatography With Flame I O N I Z a Tmentioning

confidence: 99%

“…Since organic diluents seriously reduce the method sensitivity, 2 water is usually added to the organic phase to reduce K and increase C g . 2,37 Another alternative is the addition of salt solutions, e.g., 1 mol L -1 NaCl, to promote a "salting-out" effect of residual solvents. 34,37 Diluents shall be purged with nitrogen prior to use for 3, 37 4 2 or 24 h; 34 (ii) volume of diluent in the headspace vial: larger solution volumes inside the vial (smaller β values) can reduce C g (equation 1), 2 which is not desired; (iii) headspace temperature: an increase in the headspace temperature increases C g .…”

Section: Introductionmentioning

confidence: 99%

“…2,37 Another alternative is the addition of salt solutions, e.g., 1 mol L -1 NaCl, to promote a "salting-out" effect of residual solvents. 34,37 Diluents shall be purged with nitrogen prior to use for 3, 37 4 2 or 24 h; 34 (ii) volume of diluent in the headspace vial: larger solution volumes inside the vial (smaller β values) can reduce C g (equation 1), 2 which is not desired; (iii) headspace temperature: an increase in the headspace temperature increases C g . 34 However, in case of water, the temperature is usually set to 80 ºC, i.e., 20 ºC below the water boiling point to avoid overpressure in the headspace vial.…”

Section: Introductionmentioning

confidence: 99%

“…34 However, in case of water, the temperature is usually set to 80 ºC, i.e., 20 ºC below the water boiling point to avoid overpressure in the headspace vial. 2,37,38 For diluents like DMF (b.p. 153 ºC), 35 DMSO (b.p.…”

Section: Introductionmentioning

confidence: 99%

“…9, 2012 which were similar to those reported in the literature (0.01-20 μg per vial). 37 Considering the API mass of 0.5 g per vial to be later analyzed, the limits of quantification could be expressed as 6.4 ppm for ethyl acetate, 8.8 ppm for isopropanol and 0.83 ppm for acetone.Calibration curves were then constructed for each of the three solvents, using eight data points in the mass range between the limit of quantitation and 0.5 mg, which was considered the most appropriate working range (Figure 4). After the sHS-GC-FID analysis of the five APIs (0.5 g per vial dissolved in 6 mL DMF-water, 5:1), the curves were used to determine the residual solvents in APIs (external standard calibration).…”

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confidence: 99%

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Determination of volatiles in pharmaceutical certified reference materials

Nogueira¹,

Queiroz²,

Silva³

et al. 2012

J. Braz. Chem. Soc.

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Este trabalho compara os resultados obtidos na determinação de voláteis (água e solventes residuais) em novos materiais de referência certificados (MRC) ou candidatos a MRC dos ingredientes ativos farmacêuticos (API) captopril, metronidazol, diclofenaco sódico, diclofenaco potássico e furosemida, através do uso de diferentes técnicas: perda por dessecação (LOD), titulação coulométrica tipo Karl Fisher (KF), cromatografia gasosa (injeção por headspace estático) com detector por ionização em chama (sHS-GC-FID) e com espectrômetro de massas (sHS-GC-MS), análise termogravimétrica (TGA) e espectroscopia no infravermelho próximo (NIR) com análise estatística multivariada dos resultados. As três primeiras técnicas levaram a resultados complementares na determinação de voláteis, enquanto as outras duas mostraram pouca sensibilidade para a determinação de voláteis na faixa de concentração avaliada. A perda por dessecação foi considerada a técnica mais apropriada para determinação da fração mássica de voláteis a ser utilizada no cálculo do teor de API por balanço de massa.This work compares the results obtained for the determination of volatiles (water and residual solvents) in new certified reference materials (CRM) or candidate CRMs of the active pharmaceutical ingredients (API) captopril, metronidazole, sodium diclofenac, potassium diclofenac and furosemide, by means of different techniques: loss on drying (LOD), Karl Fischer (KF) coulometric titration, static headspace gas chromatography with flame ionization detection (sHS-GC-FID) and with mass spectrometry (sHS-GC-MS), thermogravimetric analysis (TGA) and near infrared spectroscopy (NIR) with multivariate chemometric analysis of results. The first three methods led to complementary results. The two other techniques were not sufficiently sensitive to determine volatiles in the concentration range evaluated. The loss on drying method was considered the most appropriate to determine the mass fraction of the volatiles to be used in the mass balance calculation of the API mass fraction in the pharmaceutical CRMs.Keywords: volatiles, water, residual solvents, active pharmaceutical ingredient (API), certified reference materials (CRM), analytical quality control IntroductionSeveral are the reasons for determining the mass fractions of water and residual solvents in pharmaceuticals, including their influence on the physicochemical 1-7 and microbiological stability of raw materials and finished products, their potential toxicity [1][2][3]8 and also economic aspects 9 since their presence results in analyte mass fractions smaller than 100%. Residual solvents may be introduced in active pharmaceutical ingredients (API) during their synthesis, especially if the final purification step is carried out by crystallization in different solvents, as well as during drug products formulation and manufacturing. 1,7,8 In the particular case of certified reference materials (CRM) of APIs, the determination of volatiles is essential both to demonstrate the compliance with Pharmacopeial acc...

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Section: Static Headspace Gas-chromatography With Flame I O N I Z a Tmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Determination of volatiles in pharmaceutical certified reference materials

Nogueira¹,

Queiroz²,

Silva³

et al. 2012

J. Braz. Chem. Soc.

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Determination of Residual Solvents in Pharmaceuticals by Static Headspace Gas Chromatography Using Natural Deep Eutectic Solvents as Mediums: A Partition Coefficients Study

2019

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Development and validation of residual solvent determination by headspace gas chromatography in Imatinib Mesylate API

et al. 2019

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An accurate, precise, robust and sensitive method was developed for residual solvents determination by fast static headspace gas chromatography (HSGC) with flame ionization detector in Imatinib Mesylate API. Residual solvents in drug substances are quantified using gas chromatography with headspace. As per regulatory guidelines, residual solvents must be controlled for release any batches of active pharmaceutical ingredients (API). This paper includes the development and validation of HSGC method for the determination of residual solvents specifically methanol, acetone, dichloromethane, n-hexane, ethyl acetate and pyridine in Imatinib Mesylate API. Imatinib Mesylate is a specific inhibitor of BCR-ABL tyrosine kinase. DB-624 capillary column, 30 m long × 0.53 mm internal diameter, the 3 µm film thickness was used for analysis. To minimize degradation, injector temperature was set at 170 °C. The initial oven temperature was kept at 35 °C for 2 min and used ramp 1 at a rate of 4 °C min −1 to temperature of 80 °C hold for 0 min and used ramp 2 at a rate of 40 °C min −1 to a final temperature of 230 °C for 12 min hold time. Nitrogen was selected as a carrier gas. 1-Methyl-2-Pyrrolidinone (NMP) was used as a sample solvent. The method can be readily used to determine defined residual solvents present in a various range of APIs, intermediates, excipients and drug products.

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Static headspace gas chromatography of (semi-)volatile drugs in pharmaceuticals for topical use

Cited by 24 publications

References 22 publications

Determination of volatiles in pharmaceutical certified reference materials

Determination of volatiles in pharmaceutical certified reference materials

Determination of Residual Solvents in Pharmaceuticals by Static Headspace Gas Chromatography Using Natural Deep Eutectic Solvents as Mediums: A Partition Coefficients Study

Development and validation of residual solvent determination by headspace gas chromatography in Imatinib Mesylate API

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