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

Abstract

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.

An orthogonal approach for method development and validation of three potential halo alkyl alcohol genotoxic impurities in miglitol drug substance by fast gas chromatography–mass spectrometry

“…Analytical methods are available for assay and related substance determination of miglitol [10][11][12][13][14][15][16][17][18][19]. Many researchers had performed quantitative determination of genotoxic impurities in different drug substances by using HPLC, UPLC, GC, IC, GC-MS, and LC-MS techniques [20][21][22][23][24][25][26][27][28]. As per the authors' knowledge, this is the first analytical GC-MS method for simultaneous determination of 2-chloro ethanol, 2-bromo ethanol, and 2-iodo ethanol without derivatization.…”