Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) Method for the
Determination of Manganese (Mn) in Rifalazil API.
M. Xia1, J. Forth2, S. Kinne2, J. van Duzer1
ActivBiotics Inc., 2Albany Molecular Research, Inc.
To develop and validate an Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) method for the
determination of Manganese (Mn) in rifalazil API.
This method utilized a Microwave Digestion System for sample preparation. Temperature ramp was from 25ºC to 145ºC in 2
hours, and vent time was 20 min. The radiofrequency (RF) power for ICP plasma was 1300 W. The plasma, auxiliary and
Nebulizing flow rate was set at 15 L/min, 1.0 L/min and 1.0 L/min respectively. Peristaltic pump flow rate for sample
introduction was 1.0 mL/min. Detection wavelength for Mn was 257.610 nm and resolution was set as normal. The samples
were mixed with 1 mL of concentrated HNO3 followed by 2 mL of H2O2 (50%) prior to microwave digestion. The diluent
for standards and samples in ICP analysis was 5% Nitric acid in water.
The specificity was demonstrated by comparing the emission intensity of a diluent blank (5% HNO3), a rifalazil matrix blank
and the 0.1 µg/mL Mn standard. The intensity of the two blanks were close to zero, while the intensity of 0.1 µg/mL Mn was
approximately 62 times the intensity of the diluent blank, which indicated the specificity of the method. The calibration
standards produced a linear regression with a correlation coefficient [R] of 0.9999 over a range of 0.1 µg/mL (2.5 ppm) to 4
µg/mL (100 ppm) Mn. The method precision and accuracy were determined via spiking rifalazil matrix blank with known
concentrations of Mn. The percent recovery of Mn at 0.1 µg/mL, 0.8 µg/mL and 4.0 µg/mL were 95.0%, 101.9% and 98.9%
respectively. The RSD for six measurements of three matrix blanks, each spiked at 0.8 µg/mL level were 0.23%, 0.43% and
0.33% respectively. The RSD obtained from a second analyst (intermediate precision) for the result of each set of data and
the two combined sets were 0.23%, 0.38%, 0.48% and 4.08% respectively. The LOD and LOQ were 0.04 µg/mL (1 ppm)
and 0.1 µg/mL (2.5 ppm) respectively.
This method was demonstrated to be specific, sensitive, accurate and reliable.