Nitrosamine impurities in angiotensin II receptor antagonists (sartans) containing a tetrazole group represent an urgent concern for active pharmaceutical ingredient (API) manufacturers and global regulators. Regarding safety, API manufacturers must develop methods to monitor the levels of each nitrosamine impurity before individual batch release. In this study, we developed and validated a sensitive, selective, and high-throughput method based on headspace gas chromatography–mass spectrometry (HS-GC–MS) for the simultaneous determination of four nitrosamines in losartan potassium API with simple sample preparation. N -Nitrosodimethylamine (NDMA, m/z 74), N -nitrosodiethylamine (NDEA, m/z 102), N -nitrosoethylisopropylamine (EIPNA, m/z 116), and N -nitrosodiisopropylamine (DIPNA, m/z 130) levels were quantified using an electron impact, single quadrupole mass spectrometer under a selected-ion-monitoring acquisition method. The method was validated according to the Q2(R1) ICH guidelines. The calibration curves of the assay ranged from 25 to 5000 ng/mL with limits of quantitation of 25 ppb for NDMA and NDEA and 50 ppb for DIPNA and EIPNA. The accuracy of the developed method ranged from −7.04% to 7.25%, and the precision %CV was ≤11.5. Other validation parameters, including specificity, stability, carryover, and robustness, met the validation criteria. In conclusion, the developed method was successfully applied for the determination of nitrosamines in losartan potassium APIs.

A stability-indicating reversed-phase ultra-performance liquid chromatographic (UPLC) method for quantitative analysis of curcumin diethyl disuccinate (CDD) in raw materials was developed for applications in product development and quality control. Chromatographic separation was performed using the Waters ACQUITY UPLC® H-Class system consisting of an ACQUITY UPLC® BEH C18 (1.7 μm, 2.1 × 50 mm) column and a photodiode array detector set at a wavelength of 400 nm. The mobile phase consisting of 2%v/v acetic acid in water and acetonitrile was delivered at a flow rate of 0.3 mL/min under gradient elution program. The method was validated according to the ICH Q2(R1) guideline for the validation of analytical procedures. The method was found to be linear over the concentration range of 8–12 μg/mL with the coefficient of determination >0.995. The accuracy of the method established as %recovery ranged from 98.3 – 100.8%. The precision of the method expressed as %CV was found to be <1%. The coelution of degradation products from six stress test conditions was not observed. The method was robust under the variation of chromatographic parameters. The method was successfully applied in the determination of CDD content in raw materials.