Page 71 - Pharmaceutical Solution for Pharma Analysis

LAAN-A-CP-E012"

Application Inductively Coupled Plasma Atomic Emission Spectrometry

News Analysis by ICP Atomic Emission Spectrometry in

Accordance with the ICH Q3D Guideline for Elemental
No.J99" Impurities Using ICPE-9820

Q Introduction QOutline of the ICH Q3D Guideline for Elemental
Analysis of elemental impurities is one of the safety Impurities
assessments required in the field of pharmaceuticals. In In the ICH Q3D Guideline for Elemental Impurities, 24
Japan, residual metal catalysts are classified as inorganic elemental impurities were identified as elements of
impurities according to the guidelines for Impurities in concern due to their toxicity, and permitted daily
New Drug Substances (No. 1216001, issued by the exposure limits (PDE) were established. The elements
Evaluation and Licensing Division, the Pharmaceutical include lead (Pb), cadmium (Cd), mercury (Hg), and
and Food Safety Bureau, the Japanese Ministry of arsenic (As), referred to as the "big four," as well as
Health, Labour and Welfare), and are to be detected residual metal catalysts added intentionally in the
appropriately according to the method specified in the synthesis of a drug substance. Table 1 shows the
Japanese Pharmacopoeia, and evaluated at the stage of ICH Q3D Guideline (STEP4).
drug development. At the International Conference on As permitted exposure values for the elemental
Harmonisation of Technical Requirements for impurities have been set as PDE values, the PDE values
Registration of Pharmaceuticals for Human Use: ICH, must be converted to concentrations to evaluate the
various guidelines were established and harmonized elemental impurity components in the formulations or
between Japan, Europe, and the US, including their component substances. As calculation methods,
guidelines for elemental impurities in pharmaceuticals, options 1, 2a, 2b, and 3 are available. Therefore, as
referred to as the ICH Q3D, Guideline for Elemental long as the formulation is appropriate for the PDE value
Impurities. of the elemental impurity, any of the methods may be
For the analysis of elemental impurities, the methods selected. Calculation examples for the respective
specified for use as general analytical methods in the options are shown in Table 2 to Table 5.
First Supplement of the Sixteenth Edition of the
Japanese Pharmacopoeia include inductively coupled
plasma atomic emission spectrometry (ICP-AES),
inductively coupled plasma mass spectrometry (ICP-
MS), and atomic absorption spectrometry. Of these,
ICP-AES is the most convenient, offering quick and easy
multi-element analysis, and low running costs.
Here, we conducted analysis of 24 elements according
to the ICH Q3D guidelines using the Shimadzu ICPE-
9820 multi-type ICP atomic emission spectrometer. The
ICPE-9820 offers simultaneous all element analysis with
high sensitivity and high precision, while delivering high
throughput. Low running costs are achieved by a
unique combination of the reduced-flow mini-torch and
vacuum optics, thereby reducing the overall
consumption of argon.

Table 1 Permitted Daily Exposure for Elemental Impurities of ICH Q3D (STEP4)
Oral Parenteral Inhalation Oral Parenteral Inhalation
Class Element Class Element
μg/day μg/day μg/day μg/day μg/day μg/day
As 15 15 2 Pt 100 10 1
Cd 5 2 2 Se 150 80 130
1
Hg 30 3 1 2B Rh 100 10 1
Pb 5 5 5 Ru 100 10 1
Co 50 5 3 Tl 8 8 8
2A Ni 200 20 5 Ba 1400 700 300
V 100 10 1 Cr 11000 1100 3
Ag 150 10 7 Cu 3000 300 30
Au 100 100 1 3 Li 550 250 25
2B Ir 100 10 1 Mo 3000 1500 10
Os 100 10 1 Sb 1200 90 20
Pd 100 10 1 Sn 6000 600 60