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

Anerao, Ajit; Patil, Bhushan; Pradhan, Nitin

doi:10.22159/ijpps.2018v10i8.27670

Cited by 4 publications

(4 citation statements)

References 7 publications

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“…Anerao et al reported that if a large volume of a test sample is introduced into the GC column it can get damage in the long run so to overcome this problem headspace injector is preferred. They also reported in their finding that the sensitivity of a flame ionization detector is not sufficient while analyzing impurities at a low concentration which creates a challenge when analyzing some impurities to overcome this problem pre-column derivatization technique is required before carrying out the analysis [47]. The problems in GC-MS analysis is given in Table 4.…”

Section: Challenges In Gc-ms Analysismentioning

confidence: 99%

A Review on Analytical Challenges in Monitoring and Controlling Genotoxic Impurities

Sutnga¹,

R²

2020

Asian J Pharm Clin Res

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Genotoxic impurities (GIs) are chemical agents that have a DNA-interaction characteristic which can ultimately lead to cancer. Their presence in various drug substances had driven various regulatory authorities to guide monitor, control, and to limit their level in various drug products. The objective of this article is to review the analytical approaches and challenges faced while accessing, monitoring, and controlling GIs in pharmaceuticals and also a brief explanation such as low limits of GIs, matrix interference, non-volatility, and environmental conditions encountered during the analysis of GIs are also discussed in this paper. At present, several modern analytical techniques are being used for the analysis of GIs such as high-performance liquid chromatography, liquid chromatography-mass spectrometry, and gas chromatography-mass spectroscopy that have high selectivity and sensitivity, but at the same time, many researchers have reported several challenges while using these techniques. Impacts of GIs are very important and various international organizations such as the World Health Organization have set out rules for regulating these chemicals. Hence, we can conclude that analytical approaches and their challenges are essential to understand because they play a key role to develop robust analytical methods.

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Section: Challenges In Gc-ms Analysismentioning

confidence: 99%

A Review on Analytical Challenges in Monitoring and Controlling Genotoxic Impurities

Sutnga¹,

R²

2020

Asian J Pharm Clin Res

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“…Most reported methods were for the detection of DMS in various types of active pharmaceutical ingredient (API). These include gas chromatography–flame ionization detector (GC–FID) analysis of DMS in a hydrophobic API by dissolving in hexane (Seymour, 1980), GC‐mass spectrometry (MS) analyses of DMS in pantoprazole sodium via direct injection (Raman et al, 2008), liquid–liquid extraction from an aqueous soluble API using methyl tert butyl ether followed by GC–MS analyses (Rahman et al, 2017; Zheng et al, 2009), derivatization in ionic liquid media and analysis by liquid chromatography‐MS (Grinberg et al, 2013), pre‐column derivatization followed by headspace GC–FID analysis in Methoxsalen, a drug substance (Anerao et al, 2018), DMS detection in methyl ester sulfonate by Drager tube procedure (Khan et al, 1997) and hexane extraction from methyl ester sulfonate followed by GC–MS analysis (Bonnie & Aziz, 2019). There was also a report of detecting DMS which can be a by‐product from synthesis of methyl ester sulfonate using GC–MS (Bonnie & Aziz, 2019).…”

Section: Introductionmentioning

confidence: 99%

A GC–MSD method for analysis of dimethyl sulfate in palm oil‐based esterquat

Tay

Aziz

Maurad

2023

J Americ Oil Chem Soc

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Dimethyl sulfate (DMS) is a quarternizing agent for esteramine used for the synthesis of esterquat. To date there is no reliable published method for quantification of DMS in palm‐based esterquat. Esterquat is used in the formulation of personal care and textile cleaning. The process of quaternization is usually incomplete and there will be unreacted DMS. This work presents a new simple method involving solvent extraction of DMS followed by analysis with gas chromatography–mass spectrometry detector to quantify the unreacted DMS. This method was validated as per International Council for Harmonization requirements. This novel method showed good repeatability (relative standard deviation [RSD] < 5%) and inter‐day with different analyst reproducibility (RSD < 5%). The limits of detection and quantification were 5 and 10 μg mL−1, respectively. The accuracy of the method was evaluated by the analysis of spiked samples and it was found that good recovery was found at spiking levels of 20, 30, and 50 μg mL−1 with % recovery falling within the 80%–120% acceptable limit. However, at 10 μg mL−1, the percentage recovery was slightly below the recommended limit.

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“…Very few reports are available in the literature on the determination of DMS in Esomeprazole magnesium drug and its impurities. Some of the methods for DMS determination by different techniques [6][7][8][9][10][11][12][13][14][15] on different drug substances. The literature survey on DMS Content did not reveal analytical methods for determining dimethyl sulphate impurity in any pharmaceutical drug containing a salt form.…”

Section: Introductionmentioning

confidence: 99%

Method Development and Validation of Dimethyl Sulphate Content in Esomeprazole Magnesium Drug Substance by Gc-MS

Perla,

Gandhi,

Jagadeesh

et al. 2023

J App Pharm Sci Res

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Dimethyl sulfate is universally used as an alkylating, sulfating and sulfonating agent in organic synthesis; hence it is one of the probable impurities during the synthesis of the esomeprazole magnesium. As per ICH M7, it is genotoxic and mutagenic, so it needs to be controlled as per the acceptable intake of dimethyl sulfate and daily sample dosage. This method validation can be achieved by the hyphenated technique of gas chromatography with mass spectroscopy, which is used to develop the dimethyl sulfate impurity in esomeprazole magnesium drug substance containing salt. The method is achieved with a DB-1 column with electron impact ionization source in sim mode ion under electronic pneumatic pressure control and deliberate oven ramp programming temperature was used. A dissolved, extracted and auto-injection sample was implemented for sample introduction in a splitless mode. Dichloromethane and 2N NaOH was used as a diluent. The calibration curve showed good linearity over the 1.69 to 8.40 ppm (limit: 5.56 ppm) and its correlation coefficient was >0.999. A limit of detection 0.50 ppm and limit of quantitation 1.69 ppm was achieved when the samples were prepared at 50 mg/mL. While recovery proved to be 106.8 to 113.5%, hence it signified the matrix effect.

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

Cited by 4 publications

References 7 publications

A Review on Analytical Challenges in Monitoring and Controlling Genotoxic Impurities

A Review on Analytical Challenges in Monitoring and Controlling Genotoxic Impurities

A GC–MSD method for analysis of dimethyl sulfate in palm oil‐based esterquat

Method Development and Validation of Dimethyl Sulphate Content in Esomeprazole Magnesium Drug Substance by Gc-MS

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