Microcolumn Liquid Chromatography-Atmospheric Pressure Chemical Ionisation Tandem Mass Spectrometric Determination of Nitrosamine Impurities From Pharmaceutical Products.

RATIONALE: Pharmaceutical analysis is vital for assessing drug quality and identifying impurities. The recent emergence of carcinogenic nitrosamine contaminants has escalated scrutiny, resulting in the withdrawal of multiple medications. This study focuses on developing robust analytical techniques to detect specific nitrosamine impurities in anticoagulant drugs (Apixaban, Rivaroxaban) and antidepressant drugs (Duloxetine HCl) while enhancing the eco-friendliness of the method.

METHODS

Nitrosamines were separated on a microbore liquid chromatographic column, and their concentrations were determined using a liquid chromatography system coupled to a triple quadrupole tandem mass spectrometer in positive/negative mode with atmospheric pressure chemical ionisation.

RESULTS

The results showed good separation of analytes with sensitivities reaching the required standards. The method was validated as per ICH Q2(R2) guidelines. The linearity of the method was performed from 0.1 ng/g to 5 μg/g quantity of the nitrosamines. The obtained calibration curves showed excellent linearity with the square of regression coefficient ranging from 0.994 to 0.998. The determination accuracy ranged from 85.53% to 119.55%, with a relative standard deviation of 2.3% to 8.1%. The interday and intraday precisions were less than 10%. The findings illuminate intricate relative uncertainties ranging from 18.2% to 29.5% across three drug products. Regarding sustainability, the method scored 69 on the GAPI assessment and 0.67 on the AGREE assessment, indicating moderately green.

CONCLUSION

This validated method provides sensitivity and precision in detecting nitrosamine impurities in the selected pharmaceutical products in the limits specified by various pharmacopeias and compliant with ICH Q2 (R2) standards. The solvent consumption is relatively very low compared with that of the reported standard methods; hence, the method becomes environmentally friendly and economical.