ABSTRACT
The study was designed to establish a 2D UPLC-QTOF method to extrapolate the structure of an unknown substance in carboplatin injection and its relationship with the excipient. By using phenyl-hexyl column (250 mm×4.6 mm, 5 μm) with mobile phase consisting of tetrabutylammonium sulfate buffer (pH 7.5) and acetonitrile in gradient elution mode, an unknown impurity in carboplatin injection was found and quantitatively determined. Then a 2D UPLC-QTOF, HSS T3 column (100 mm×2.1 mm, 1.7 μm) was employed to confirm the molecular weight and the structure of the unknown impurity (electrospray ionization source, positive ion mode, MSE mode) with mobile phase consisting of 0.1% formic acid and acetonitrile. The relationship among impurities, API and excipient was investigated by accelerated stability test with ICP-MS/MS, ICP-AES. Results showed that disodium edetate in the formulation interacted with carboplatin producing an unknown impurity containing platin, and induced the increase of 1,1-cyclobutanedicarboxylic acid. The research should be done on the rationality of the addition of disodium edetate in such injections containing heavy metals.
ABSTRACT
Objective To establish a high performance liquid chromatography (HPLC) method for the determination of disodium edentate (EDTA-2Na) in nalmefene hydrochloride injection. Methods Content of EDTA-2Na in nalmefene hydrochloride injection was determined by HPLC. C18 Column was used. The mobile phase consisted of 0.3% tetrabutylammonium hydroxide solution-wateracetonitrile (20: 45: 35) with a flow rate of 1.0 ml/min, and the detection wavelength was 254 nm. The column temperature was 30°C and the injection volume was 20 µl. Results The quantification limit and detection limit were 0.199 and 0.060 µg/ml, respectively; the linear equation for the disodium edetate was Y=10.125X-0.216, and the calibration curves were linear within the range of 2.4593~ 7.3780 µg/ml (r=1.000). Each concentration of the average recovery was between 98~102% (n=9) (RSD%=0.58%). Conclusion The method can be used for the determination of EDTA-2Na in nalmefene hydrochloride injection, which is convenient, fast, sensitive and reproducible, with good precision, specificity and accuracy.