Page 45 - Pharmaceutical- Guide to Biopharmaceutical

Quality Control

Controlling Elemental Impurities ICPMS-2030

Analysis by ICP Mass Spectrometry Specified in benefits

the ICH Q3D Guideline for Elemental Impurities Cell Line Optimization
click here • Using Shimadzu’s unique mini-torch plasma system, samples can be measured at half
the running cost of previous systems.
Operating Principle and Features Table 1 Measurement Conditions
Instrument ICPMS-2030 • The collision cell offers high sensitivity and low interference to enable simultaneous
ICP-MS systems are generally considered to offer the highest sensitivity RF power 1.2 kW measurement of all target elements evaluated.
available for elemental analysis. These systems use an inductively coupled Plasma gas flowrate 8.0 L/min
argon plasma (ICP) generated at about 10,000 °C to ionize elements in Auxiliary gas flowrate 1.1 L/min • If the Development and Diagnosis Assistant functions, an industry first, are used, Culture
liquid samples and then analyze the ions by mass spectrometry with the Carrier gas flowrate 0.60 L/min data can be analyzed in one tenth the time required previously. (Click here for the
Sample injection
Nebulizer10
ability to detect elements down to the ppt level. Chamber Cyclone chamber (electronically cooled)
Given that elemental impurities in pharmaceuticals must be Plasma torch Mini-torch assistant functions.)
controlled to very low concentrations, ICP-MS systems have been Collision gas He
attracting attention because of their high sensitivity. They also have
disadvantages, however, such as high argon gas consumption rates Table 2 Tablet Analysis Results
and high running costs. In contrast, ICPMS-2030 enables analysis at Oral Detection Limit Measurement Spiked
Spike and
Permitted
about one half the cost overall. This is because it features Shimadzu’s Preparation Concentration *1 (3 σ) Converted Value Concentration Recovery Rate
for Tablet
unique mini-torch plasma system that successfully reduces argon gas PDE Preparations *2 (in tablet) (in tablet)
consumption to 2/3 of conventional levels. Furthermore, relatively µg µg/g µg/g µg/g µg/g % Purification
inexpensive 99.99 % pure industrial-grade argon gas can be used Ag 150 750 0.001 N. D. 0.1 107
instead of 99.999 % or higher high-purity argon gas normally used for As 15 75 0.002 N. D. 0.2 101
ICP-MS analysis. Au 100 500 0.001 N. D. 0.2 91
Ba 1400 7000 0.002 0.013 0.2 96
96
0.003
25
Measurement Method and Conditions Cd 50 5 250 0.0006 N. D. 0.2 101
Co
0.4
N. D.
Cr 11000 55000 0.003 0.017 0.4 104
The ICH Q3D Guideline for Elemental Impurities specifies Permitted Daily Cu 3000 15000 0.04 0.15 0.4 102
Exposure (PDE) for 24 elements for which toxicity is a concern. We have Hg 30 150 0.006 N. D. 0.2 100
verified that ICPMS-2030 can adequately assess whether the guidelines are Ir 100 500 0.0005 N. D. 0.2 98
met. The mini-torch and low-cost industrial-grade argon gas were used. Li 550 2750 0.01 N. D. 0.2 93
One tablet (maximum daily dose of 0.20 g), 0.5 mL of hydrochloric Mo 3000 15000 0.001 N. D. 0.2 107 Characterization
acid, and 5 mL of nitric acid were placed in a quartz decomposition Ni 200 1000 0.003 0.156 0.4 101
vessel and decomposed in a microwave sample pretreatment system. Os 100 500 0.007 N. D. 0.2 92
After decomposition, 0.1 mL of hydrochloric acid was added and Pb 5 25 0.001 0.003 0.2 105
the mixture was made up to 20 mL with pure water to prepare the Pd 100 500 0.006 N. D. 0.2 104
measurement solution (100-fold dilution). Internal standard elements Pt 100 500 0.003 N. D. 0.2 99
Sc, Ga, Y, and Te were also added during that process (to a 10 μg/ Rh 100 500 0.0008 0.003 0.2 101 Specifications
0.002
100
500
N. D.
L concentration of the measurement solution). Spike-and-recovery Ru 1200 6000 0.0009 0.007 0.2 98
Sb
98
0.2
test solutions were prepared by adding measurement elements to the Se 150 750 0.01 N. D. 0.2 98 Instrument: ICPMS-2030
decomposed sample. Sn 6000 30000 0.002 N. D. 0.2 98 Quality Control
The calibration curve method with the internal standard method was Tl 8 40 0.0005 N. D. 0.2 103 Plasma ion source unit Spray chamber: Cyclone chamber (Thermoelectric cooling type)
used to quantitatively analyze and perform a spike-and-recovery test V 100 500 0.002 N. D. 0.4 100 Peristaltic pump: 4-channel
for the 24 elements subject to the ICH Q3D guideline according to the
measurement conditions shown in Table 1. *1 Permitted concentration PDE level based on a daily intake of 0.2 g, which refers to Plasma torch: Mini-torch plasma system
a permitted concentration for oral preparations Nebulizer: Coaxial
Results *2 Detection limit converted for tablet Detection limit in measured solution (3 σ) × Dilution ratio Torch position adjustment: X, Y, Z-axes automatic adjustment
(100)
preparations (3 σ)
N.D. Not detected
For many of the elements, the concentration measurement value was RF power supply unit Frequency: 27 MHz
“N.D.”, but concentration was nevertheless confirmed down to at High-frequency output: Max. 1.4 kW ± 0.3 %
least four digits below the permitted concentration. Recovery rates Pharmacokinetics
for each added element were also good, which clearly shows that Application Examples Mass spectrometer unit Mass analyzer: Quadruple type mass spectrometer
measurements were performed correctly (Table 2). Mass range: 5 to 260
• Measuring hazardous elements in public drinking water Collision cell: Octopole collision cell
Conclusion • Analyzing hazardous elements and minerals in foods Helium gas 0 to 10 mL/min
• Analyzing components in blood
With the ICPMS-2030 system, the 24 elements subject to the ICH Q3D • Evaluating the safety of pharmaceuticals Detector: Electron multiplier
Guideline can be analyzed quickly and accurately at half the running Exhaust system: 3-stage operation exhaust
cost of conventional systems. Others
Dimensions: W 870 mm × D 645 mm × H 587 mm
(excluding protrusion)
Weight: 145 kg
44 45
index index