Determination of sulfonate ester genotoxic impurities in imatinib mesylate by gas chromatography with mass spectrometry

Huang, Lin; Wu, Zhiguo; Chang, Chuanyou; Yang, Zhidong

doi:10.1002/jssc.201600389

Cited by 13 publications

(10 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The complete synthetic scheme of DAPO There are few methods reported in the literature for determination of EMS using gas chromatography (GC) with flame-ionization detector (FID) and mass analyzer. Some of the reported GC methods involve direct determination of EMS [8][9][10][11], while the reminaing involve derivatization of EMS using different reagents [12,13]. The reported GC methods couple with FID or mass analyzer for direct determination of EMS were found to have less sensitivity and higher injection volumes which are not ideal for regular GC analysis.…”

Section: Introductionmentioning

confidence: 99%

Liquid chromatography-tandem mass spectrometric method for trace quantification of ethyl methanesulfonate: a genotoxic impurity in dapoxetine hydrochloride

2021

View full text Add to dashboard Cite

Background Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor drug for treating premature ejaculation. This study was designed to develop and validate a sensitive and selective LC–MS/MS method for trace analysis of genotoxic impurity ethyl methanesulfonate in Dapoxetine hydrochloride. Results Chromatographic separation was achieved on the Shodex RSpak DS-413 column, 150 × 4.6 mm, 3.0 µm using eluent containing a equal volumes of acetonitrile and 0.1% v/v formic acid in water was used in the isocratic elution mode at a pump flow of 1.0 mL/min. No interference was observed at the retention time of ethyl methanesulfonate, indicating that the developed method is specific and selective for trace level quantification.The developed method was found to be linear in the concentration range of 1–50 ppm with coefficient of regression of 0.9997. Detection limit and quantification limit were determined to be 0.6 ppm and 1.0 ppm respectively. Acceptable RSD values (< 10.0%) and recovery results (> 90%) obtained from the accuracy and precison experiments indicate that the developed method is precise and accurate in the concentration range of 1–50 ppm. Ethyl methanesulfonate solutions were stable for two days when stored at room and refrigerated temperatures. Conclusion The developed method has the ability to quantify ethyl methanesulfonate in dapoxetine hydrochloride. Thus, the anticipated method has high probability to adopt in the quality testing laboratories of pharmaceutical industry.

show abstract

Section: Introductionmentioning

confidence: 99%

Liquid chromatography-tandem mass spectrometric method for trace quantification of ethyl methanesulfonate: a genotoxic impurity in dapoxetine hydrochloride

2021

View full text Add to dashboard Cite

show abstract

“…Considering the differentiated volatility of sulfonate esters, gas chromatography- (GC-) based and liquid chromatography- (LC-) based methods have been developed. Methyl, ethyl, and isopropyl mesylate esters in APIs or final products have mostly been quantified by gas chromatography-mass spectrometry (GC-MS) [4–6]. A high-performance liquid chromatography-ultraviolet (HPLC-UV) method with derivatization has been utilized to determine methyl and ethyl methanesulfonates in methanesulfonic acid with a LOQ of 0.6 ppm [7].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Determination of 15 Sulfonate Ester Impurities in Phentolamine Mesylate, Amlodipine Besylate, and Tosufloxacin Tosylate by LC-APCI-MS/MS

Jin

Guo

Zhang

et al. 2019

Journal of Analytical Methods in Chemistry

View full text Add to dashboard Cite

Sulfonate esters have been recognized as potential genotoxic impurities (PGIs) in pharmaceuticals. An LC-MS/MS method was developed and validated for the simultaneous determination of 15 sulfonate esters, including methyl, ethyl, propyl, isopropyl, and n-butyl esters of methanesulfonate, benzenesulfonate, and p-toluenesulfonate in drug products. The method utilized atmospheric pressure chemical ionization (APCI) in multiple reaction monitoring (MRM) mode for the quantitation of impurities. The method employed an ODS column as the stationary phase and water-acetonitrile as the solvents for gradient elution without derivatization steps. The method was specific, linear, accurate, precise, and robust. Recoveries of the sulfonic esters from three drug matrices were observed in the range of 91.6∼109.0% with an RSD of not greater than 17.9% at the concentration of the LOQ and in the range of 90.4%∼105.2% with an RSD of not greater than 7.1% at the concentration of 50 ng/mL for the methanesulfonates and 10 ng/mL for the benzenesulfonates and p-toluenesulfonates. The LOD was not greater than 15 ng/mL, 2 ng/mL, and 1 ng/mL for the methanesulfonate, benzenesulfonate, and p-toluenesulfonate esters, respectively. This method was sufficiently sensitive to detect the 15 PGIs in the phentolamine mesylate tablet, amlodipine besylate tablet, and tosufloxacin tosylate tablet. This analytical method is a direct, specific, rapid, and accurate quality control tool for the determination of the 15 sulfonate esters that are most likely to exist in drug products.

show abstract

“…Genotoxic impurities (GTIs) can act as carcinogenic agents in people by initiating hereditary transformation, chromosomal breakups and modifications . In this way, an entry of impurities in low levels exhibits in the ultimate step of API, which initiates toxic effect . As indicated by the international agencies the utilization of genotoxic impurity is limited to 1.5 µg/day .…”

Section: Introductionmentioning

confidence: 99%

Application of simple and sensitive LC‐MS/MS approach for trace level quantification of potential genotoxic impurities in lamivudine salicylate formulations

Ganji

Gopireddy

2019

Separation Science Plus

View full text Add to dashboard Cite

A new liquid chromatography with tandem mass spectrometry systematic procedure was envisaged for determination of l‐menthol glyoxylate and (1R,2S,5R)‐menthyl‐5(R,S)‐acetoxy‐(1,3)‐oxathiolane‐2(R)‐carboxylate, the potential genotoxic impurities in lamivudine salicylate drug formulation. The process describes an effective use of Hypersil BDS C8 (50 mm × 4.6 mm, 3.0 µm) column retained at 40°C and positive ion electrospray ionization in multiple reaction‐monitoring mode for quantification of two genotoxic impurities. The mobile phase comprises of 60:40 ratio of 5 mM ammonium formate and combination of acetonitrile/methanol (50:50 v/v) pumped at the flow rate of 0.5 mL/min with run time 10 min. This approach was validated for robustness, reproducibility, precision, linearity, accuracy, limit of detection and limit of quantification by following ICH guidelines. The established approach is able to assess two genotoxic impurities at 0.3 ppm (LOQ) against to 2.0 mg/mL of lamivudine. The linearity of this approach is found to 0.3–10.0 ppm, which meets the quantified accepted level (5.0 ppm) in LOQ‐200% range with the correlation coefficients of 0.999 and 0.997. Accuracy was arrived between 98.7–103.1%. The validated method could be highly useful as a good quality assessment tool for quantitation of genotoxic impurities in lamivudine formulation.

show abstract

Determination of sulfonate ester genotoxic impurities in imatinib mesylate by gas chromatography with mass spectrometry

Cited by 13 publications

References 15 publications

Liquid chromatography-tandem mass spectrometric method for trace quantification of ethyl methanesulfonate: a genotoxic impurity in dapoxetine hydrochloride

Liquid chromatography-tandem mass spectrometric method for trace quantification of ethyl methanesulfonate: a genotoxic impurity in dapoxetine hydrochloride

Simultaneous Determination of 15 Sulfonate Ester Impurities in Phentolamine Mesylate, Amlodipine Besylate, and Tosufloxacin Tosylate by LC-APCI-MS/MS

Application of simple and sensitive LC‐MS/MS approach for trace level quantification of potential genotoxic impurities in lamivudine salicylate formulations

Contact Info

Product

Resources

About