An Orthogonal Approach for Determination of Acetamide Content in Pharmaceutical Drug Substance and Base-Contaminated Acetonitrile by GC and GC-MS External Method

Abstract

Acetamide is a potential genotoxic impurity; it should control in drug substance based on daily dosage level. It forms from base-contaminated acetonitrile and by-product of some drug substances. The available methods for acetamide in drug substance and water samples were determined by GC-MS using internal standard with critical procedures. These developed and validated methods can assist in evaluating the reaction between acetonitrile and different bases and also determine trace level acetamide in drug substances. The method development was initiated with DB-624, 30 m, 0.32 width and 1.0-μm column. The column was used to validate at the 600 ppm TTC value. Similarly, the CP-SIL 5CB, 60 m, 0.32 width, the 5-μm column was used for the remaining TTC values. The validation study was performed for all TTC limits. The % RSD for precision at 600, 60, 20, 10 and 2.5 ppm was <15%. The % recovery at all TTC level was in between the 70 and 130%. Solution stability study was performed up to the 24 h. At 2.5 ppm, the results were <15% variation from the initial value. The linearities from the 50 to 150% concerning TTC values were more than limit of 0.98 correlation coefficient. The limit of detection and limit of quantitation values were 0.4 to the 1.3 ppm, respectively, for 2.5 ppm TTC limit method.

Volatiles from cotton aphid (Aphis gossypii) infested plants attract the natural enemy Hippodamia variegata

“…The compounds were identified by comparing their retention times and mass spectra with those available in the NIST17 library (National Institute of Science and Technology software, USA). The external standard approach was employed to quantify the relative content of each identified volatile within the collected samples, following the previous protocol ( Rajana et al., 2019 ). Briefly, the standard solutions (1, 10, 50, 100, and 1000 ng/μl) of each compound were prepared in n-hexane ( Supplementary Table S1 ).…”

A Primer for Pharmaceutical Process Development Chemists and Analysts in Relation to Impurities Perceived to Be Mutagenic or “Genotoxic”

“…A PDE value of 7.1 mg (Table ) was determined for acetamide by Bercu et al on the basis of ICH M7­(R1) criteria for a nonmutagenic carcinogen. Given the magnitude of the PDE, 4733 times higher than the default lifetime TTC value of 1.5 μg/day, there is no clear rationale for developing a highly sensitive assay of the type described by Rajana et al…”

“…A PDE value of 7.1 mg (Table 6) was determined for acetamide by Bercu et al 8 on the basis of ICH M7(R1) criteria for a nonmutagenic carcinogen. Given the magnitude of the PDE, 4733 times higher than the default lifetime TTC value of 1.5 μg/day, there is no clear rationale for developing a highly sensitive assay of the type described by Rajana et al 92 In a 2017 publication on the analysis of potentially genotoxic impurities in pantoprazole sodium drug substance, Subbaiah et al 93 listed the substance N-(4-hydroxyphenyl)acetamide as GTI-A. In fact, GTI-A is paracetamol (4′-hydroxyacetanilide), which is the most commonly used analgesic and antipyretic worldwide.…”

Quantitative method for determination of 3,3‐dimethylallyl bromide genotoxic impurity in Tazarotene drug substance by GC‐MS

“…As per author cognizance, no analytical method was available in the literature for determination of 1-bromo-3 methyl -2-butene/3,3-dimethylallyl bromide at a low level (<10 ppm) in presence of tazarotene drug substance and drug product. Based on earlier experience on quantification of genotoxic impurities in different drug substances, the quantitative method was developed for the determination of 3,3-dimethylallyl bromide genotoxic impurity in tazarotene drug substance by GC-MS [14][15][16]. Many other analytical methods were available to determine the genotoxic impurities by LC-MS/MS and GC-MS [17][18][19][20][21][22][23][24][25][26][27][28][29].…”