ABSTRACT
@#TA method for the content determination of methionine sulfoxide and methionine sulfone in compound amino acid injection (18AA-II) was established in order to investigate their level in 155 batches of this product, and to explore the reason for the generation of these two impurities.The determination was performed on an Agilent Poroshell 120 EC-C18 column with mobile phases of sodium acetate/tetrahydrofuran solution (A) and sodium acetate solution -acetonitrile-methanol (B, 200∶400∶400) (gradient elution) at the flow rate of 0.5 mL/min.The excitation wavelength and the emission wavelength of the fluorescence detector were 233 nm and 441 nm, respectively.The column temperature was 40 °C, and the injection volume was 8 μL.The contents of methionine sulfoxide and methionine sulfone from 155 batches of compound amino acid injection (18AA-II) was determined using this method, and the residual oxygen content was detected by headspace gas analyzer.The results showed that the linear range of methionine sulfoxide and methionine sulfone were 0.128 1-10.250 0 μg/mL (r = 0.999 9) and 0.261 0-10.440 0 μg/mL (r = 0.999 8), respectively.The limits of quantitation were 0.13 μg/mL and 0.26 μg/mL, respectively; the limits of detection were 0.04 μg/mL and 0.09 μg/mL, respectively.RSDs of precision, stability and repetitive test were all lower than 1.3%.The recoveries ranged 98.00%-100.79% (RSD = 1.15%, n = 9) and 98.19%-102.31% (RSD = 1.33%, n = 9).The content level of oxidized related substances from different manufacturers showed significant difference, showing relevance with the residual oxygen content to some extent, yet no significant correlation with the added amount of antioxygen (sodium pyrosulfite).The method is validated to be useful for the content control of methionine sulfoxide and methionine sulfone in compound amino acid injection (18AA-II).It is quite necessary to include the determination of oxidized related substance into the quality specification.Manufacturers should strengthen the control of remaining oxygen in their products.
ABSTRACT
OBJECTIVE： To establish a method for the content determination of 14 elements in Deproteinized calf blood extractives injection. METHODS： Inductively coupled plasma-mass spectrometry （ICP-MS） was adopted. The radiofrequency power was 1 350 W； flow rate of carrier gas （argon） and collision gas （helium） was 1.1 L/min and 4.5 L/min respectively； integration time was 1.5 s； plasma gas flow rate was 18 L/min； depth of sampling was 65 mm； speed of sampling peristaltic pump was 24.0 r/min； data sampling mode was peak-jump acquisition mode； data collection was repeated for 3 times. RESULTS： The linear ranges of Cd， Pb， As， Co， V， Ni， Tl， Ag， Mo， Cu， Cr， Ba and Al were 0.05-50 μg/L （r＝0.999 7）， 0.05-50 μg/L （r＝0.999 7）， 0.05-50 μg/L （r＝0.999 8）、0.05-50 μg/L （r＝0.999 5）， 0.05-50 μg/L （r＝0.999 5）， 0.05-50 μg/L （r＝0.999 8）， 0.05-50 μg/L （r＝0.999 6）， 0.05-50 μg/L （r＝0.999 5）， 0.05-50 μg/L （r＝0.999 5）， 0.05-50 μg/L （r＝0.999 8）， 0.05-50 μg/L （r＝0.999 6）， 0.05-50 μg/L （r＝0.999 6）， 0.05-50 μg/L （r＝0.999 7） and 0.5-70 μg/L （r＝0.999 8）， respectively. The limits of quantitation were 0.003 1， 0.008 9， 0.016 0， 0.025 0， 0.002 1， 0.006 9， 0.038 1， 0.002 1， 0.005 5， 0.002 0， 0.023 1， 0.005 0， 0.002 0， 0.324 9 μg/L， separately. The limits of determination were 0.000 9， 0.002 7， 0.004 8， 0.007 5， 0.000 6， 0.002 1， 0.011 4， 0.000 6， 0.016 5， 0.000 6， 0.006 9， 0.001 5， 0.000 6， 0.097 5 μg/L， separately. RSDs of precision， stability and repeatability tests were all less than 8％. The recoveries were 87.4％-94.3％（RSD＝2.6％， n＝9）， 110.3％-118.2％（RSD＝1.8％，n＝9）， 89.8％-99.7％（RSD＝3.1％，n＝9）， 77.7％-84.4％（RSD＝2.5％，n＝9）， 105.6％-113.4％（RSD＝2.3％，n＝9）， 106.7％-116.5％（RSD＝2.7％，n＝9）， 89.1％-104.5％（RSD＝4.5％，n＝9）， 105.6％-118.6％（RSD＝3.6％，n＝9）， 77.8％-88.0％（RSD＝4.0％，n＝9）， 106.7％-116.1％（RSD＝2.8％，n＝9）， 88.5％-97.1％（RSD＝3.1％，n＝9）， 80.5％-88.6％（RSD＝2.9％，n＝9）， 85.2％-99.4％（RSD＝4.2％，n＝9）， 97.6％-109.3％（RSD＝3.2％，n＝9）， respectively. CONCLUSIONS： The method is simple， accurate. The precision， stability and repeatability of this method are also good. It is suitable for simultaneous determination of 14 elements in Deproteinized calf blood extractives injection.