Page 73 - Pharmaceutical Solution for Pharma Analysis

Application No.J99"
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Table 5 Calculation by Option 3: Finished Product
Concentration (μg/g) = PDE (μg/day)/Daily intake of drug product (g/day)
PDE (μg) Maximum Permitted Concentration (μg/g)
Daily Intake (g) Pb As Pd Ni Pb As Pd Ni
Drug Product 2.5 5 15 100 200 2 6 40 80

Q Sample Q Analysis
· Ophthalmic solution Quantitative analysis of the 24 elements subject to the
· Tablet (Daily intake: 1 tablet (0.2 g)) ICH Q3D guidelines was conducted using the calibration
curve-internal standard method, and spike-and-recovery
testing was also conducted.

Q Sample Preparation Q Analytical Results
1. Pretreatment of sample (ophthalmic solution) Table 7 shows the results of analysis of the ophthalmic
To 2 mL of sample (approximately 2 g), add 0.5 mL solution. The PDE value of the ophthalmic solution was
hydrochloric acid, 0.5 mL nitric acid and internal used as the parenteral value. Table 8 shows the results of
standard element Y (0.5 mg/L based on measurement the tablet analysis. Good results were obtained in the
solution concentration). Adjust the volume to 10 mL spike-and-recovery testing for each of the samples (Tables
using distilled water to use as the measurement 7 and 8 ). In addition, the detection limit calculated as the
*1
solution (5-fold dilution). A spike-and-recovery test concentration in the sample (Tables 7 and 8 ) adequately
*2
solution was prepared using a similarly prepared satisfied the permitted concentrations (Tables 7 and 8 ).
*3
solution spiked with a standard solution of the
measurement element.
2. Pretreatment of tablet sample Q Conclusion
Two tablets (daily dosage of 1 tablet per day (0.20 g)) Use of the ICPE-9820 permits quick, accurate analysis
were dissolved with 3 mL hydrochloric acid and 2 mL of the 24 elements specified in the ICH Q3D guideline.
nitric acid using a microwave sample preparation
system and a sample pretreatment quartz vessel.
After conducting microwave digestion, the solution
[References]
volume was adjusted to 20 mL with distilled water to 1) Impurities in New Drug Substances (No. 1216001, issued by the
use as the measurement solution (50-fold dilution). At Evaluation and Licensing Division, the Pharmaceutical and Food
this time, the internal standard elements Y and In (Y at Safety Bureau, the Japanese Ministry of Health, Labour and
Welfare)
0.5 mg/L and In at 1.0 mg/L) were added to the
2) First Supplement of the Sixteenth Edition of the Japanese
solution. Also, prior to digestion, the measurement Pharmacopoeia
element was added to prepare a spike-and-recovery 3) ICH Q3D: Guideline for Elemental Impurities (STEP4)
test solution.

Q Instrument and Analytical Conditions
Measurement was conducted using the Shimadzu ICPE-
9820 multi-type ICP atomic emission spectrometer. The
measurement conditions are shown in Table 6.
The ICPE-9820 is a spectrometer that uses the latest
CCD, permitting simultaneous measurement of all
elements and all wavelengths, while its high-sensitivity
axial observation permits high-throughput
measurement. Further, the high-temperature plasma
generated by the mini torch assures high sensitivity with
low ionization interference to provide acquisition of
accurate values. In addition, the mini-torch plasma
produced by low-flowrate argon gas, the Eco mode
and the vacuum spectrometer greatly reduce running
costs.

Table 6 Analytical Conditions
Instrument : ICPE-9820
Radio frequency power : 1.2 kW
Plasma gas Flowrate : 10 L/min
Auxiliary gas Flowrate : 0.6 L/min
Carrier gas Flowrate : 0.7 L/min
Sample introduction : Nebulizer 10
Misting chamber : Cyclone chamber
Plasma torch : Mini-Torch
Observation : Axial (AX) / Radial (RD)