Determination of low ppm levels of dimethyl sulfate in an aqueous soluble API intermediate using liquid–liquid extraction and GC–MS

Zheng, Jie; Pritts, Wayne A.; Zhang, Shuhong; Wittenberger, Steve

doi:10.1016/j.jpba.2009.06.022

Cited by 27 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As such, sample extraction is used only as a last resort. 18 Nonetheless, it may be potentially beneficial in analysis of drug products when dealing with complex excipients. Lastly, chemical derivatization of analytes is a versatile technique that can be used to modify physicochemical properties of analytes.…”

Section: Methods Scouting and Evaluationmentioning

confidence: 99%

See 1 more Smart Citation

A Systematic Method Development Strategy for Determination of Pharmaceutical Genotoxic Impurities

Sun

Liu

Kord

2010

Org. Process Res. Dev.

View full text Add to dashboard Cite

Trace level genotoxic impurities (GTIs) in pharmaceutical products require precise, accurate, and robust analytical methodologies for their analysis and control. The need to control most genotoxic impurities to the low ppm level in combination with the very often reactive and labile nature of genotoxic impurities presents significant analytical challenges. This article reports a systematic GTI method development strategy (MDS) based on our successful experiences in GTI analysis in recent years and quality by design (QbD) principles emphasizing the expected method performance being built into the method. It starts with a predefined method goal, followed by method understanding and a risk control strategy. Due to the nature of the GTI analysis, sophisticated analytical methodologies such as chemical derivatization and mass spectrometry detection are often developed, especially in the research and development (R&D) phase of drug development. Such methods usually consist of more variables than conventional methods in pharmaceutical analysis. Therefore, sound scientific understanding and risk control strategies are of great importance to ensure the method performance for trace GTI analysis. For methods to be implemented in manufacturing quality control laboratories that are lacking sophisticated instrumentation and skilled analysts, method simplicity, robustness, and ruggedness become more prominent in addition to method accuracy. This article describes QbD approaches for developing such methods using real world case studies including dimethyl sulfate analysis of a recently approved drug, pazopanib HCl (Votrient).

show abstract

Section: Methods Scouting and Evaluationmentioning

confidence: 99%

“…However, this does not preclude their use in special cases when necessary. 18 It is worth mentioning that the three unit operations are not completely independent and should always be evaluated holistically.…”

Section: Methods Scouting and Evaluationmentioning

confidence: 99%

A Systematic Method Development Strategy for Determination of Pharmaceutical Genotoxic Impurities

Sun

Liu

Kord

2010

Org. Process Res. Dev.

View full text Add to dashboard Cite

show abstract

“…This report suggests that solution stability and diluent study need to be optimized and mass detector is necessary to get DMS sensitivity at trace level [15]. Few more methods are reported by extracting the DMS in a solvent and tested by GC-MS [16][17][18][19][20]. DMS quantification by ion chromatography technique with conductivity detector is also reported by separating ionic compounds using Allsep anion exchange column [21].…”

Section: Introductionmentioning

confidence: 99%

Determination of Residual Dimethyl Sulfate in Methoxsalen Drug Substance by Pre-Column Derivatization With Static Headspace Gas Chromatography

Anerao¹,

Patil²,

Pradhan³

2018

Int J Pharm Pharm Sci

View full text Add to dashboard Cite

Objective: Dimethyl sulfate has been highlighted as potential genotoxic and carcinogenic impurity. A sensitive Headspace gas chromatography (HS-GC) method with pre-column derivatization was developed and validated for the determination of dimethyl sulfate impurity in methoxsalen active pharmaceutical ingredient.Methods: HS-GC method on the column Agilent DB-5, 30m X 0.53 mm, film thickness 1.5 µm, with flame ionization detector (FID) was used. Derivatization reagent concentration, time of reaction and pH of the solution were optimized during method development. This analytical method was evaluated by performing method validation as per ICH guideline.Results: The proposed method was specific, linear, accurate, rugged and precise. The calibration curves showed good linearity over the concentration range of 0.5 μg/ml to 3.0 μg/ml and the correlation coefficient was 0.999. Method had very low limit of detection (LOD) and limit of quantification (LOQ) 2.0 μg/g and 5.0 μg/g respectively. Accuracy was observed within 98.1%–104.5%.Conclusion: The developed method was demonstrated to be accurate, robust and sensitive for the determination of dimethyl sulfate impurity in methoxsalen drug substance.

show abstract

“…Isolation of DMS from the matrix through different techniques prior to injection in the GC can be considered as a practical solution to the above mentioned problem. Liquid-liquid extraction of DMS with ethyl t-butyl ether has been used but limited to aqueous soluble active ingredient (AI) and intermediates with satisfactory results [7], however not so useful for aqueous insoluble compounds.…”

Section: Introductionmentioning

confidence: 99%

Determination of residual dimethyl sulfate in hexaconazole technical (fungicide) by head space gas chromatography mass spectrometry

Petha

Lokhande

Seshadri

et al. 2017

Microchemical Journal

View full text Add to dashboard Cite

Determination of low ppm levels of dimethyl sulfate in an aqueous soluble API intermediate using liquid–liquid extraction and GC–MS

Cited by 27 publications

References 29 publications

A Systematic Method Development Strategy for Determination of Pharmaceutical Genotoxic Impurities

A Systematic Method Development Strategy for Determination of Pharmaceutical Genotoxic Impurities

Determination of Residual Dimethyl Sulfate in Methoxsalen Drug Substance by Pre-Column Derivatization With Static Headspace Gas Chromatography

Determination of residual dimethyl sulfate in hexaconazole technical (fungicide) by head space gas chromatography mass spectrometry

Contact Info

Product

Resources

About