By: Daniel L. Davis and Robert H. Clifford, Ph.D.
SSI-TOC-103
Measuring Samples Per USP 26 Using Shimadzu TOC-V*W
Introduction:
The United States Pharmacopoeia has established guidelines for determining system
suitability and established the acceptance of Water For Injection (WFI) purposes and
Purified Water (PW) (USP Revision 26 Method <643>).
Shimadzu’s TOC-V*W analyzer is perfectly adapted to meet the requirements of USP
Rev. 26 Method <643>. The TOC-V*W analyzer utilizes three forms of oxidation (heat,
UV, and persulfate) to provide a low maintenance instrument with a detection limit of
0.0005 mg per liter.
USP Rev. 26:
The requirements for passing the system suitability test is to obtain results for the control
standard minus the reagent water that are within + 15% of the sucrose standard minus the
reagent water as shown in equation 1.
%R = [(rss-rw) / (rs-rw)] * 100 (equation 1)
Table 1- Key to equation 1
rss 1,4-Benzoquinone (area counts)
rs Sucrose (area counts)
rw Reagent Water (area counts)
%R Percent Recovery (%)
Samples are acceptable for Purified Water (PW) or Water For Injection (WFI) if
equation 2 is satisfied.
(Sample Area Counts) = (rs-rw) (equation 2)
Procedure:
Standard Preparation
Sucrose and 1,4-Benzoquinone were purchased from Sigma-Aldrich and prepared in the
following manner (see Tables 2, 3, 4):
First 1.187 mg of sucrose was accurately weighed out and brought to 1000 mL with
purified water; this is a 0.5000 mg per liter carbon solution. This was used as the high
standard in calibration. Second 0.7500 mg of 1,4-Benzoquinone was accurately weighed
out and brought to 1000 mL with purified water. This is also equal to a 0.5000 mg per
liter solution of carbon and was used as the system suitability check standard.
Table 2- Elemental breakdown of Sucrose: C12H22O11
Element Molar Mass # of Atoms in Sucrose Formal
(g/mol) Sucrose Mass (g/mol)
Carbon 12.01 12 144.1
Hydrogen 1.008 22 22.18
Oxygen 16.00 11 176.0
Total 342.3
Table 3- Elemental breakdown of 1,4-BQ: C6H4O2
Element Molar Mass # of Atoms in 1,4-BQ Formal
(g/mol) 1,4-BQ Mass (g/mol)
Carbon 12.01 6 72.06
Hydrogen 1.008 4 4.032
Oxygen 16.00 2 32.00
Total 108.1
Table 4 – Calculations for generation of standards
500 ppb C from Sucrose 500 ppb C from 1,4-BQ
C / Mol. wt. = 144.1 g carbon /342.3 g sucrose = C / Mol. wt. = 72.06 g carbon /108.1 g 1,4-BQ =
0.4210 0.6666
1.187 mg 1,4-BQ * 0.6666 = 0.5000 mg carbon 0.7500 mg 1,4-BQ * 0.6666 = 0.5000 mg carbon
1.187 mg sucrose = 0.5000 mg carbon 0.7500 mg 1,4-BQ = 0.5000 mg carbon
1000 mL 1000 mL 1000 mL 1000 mL
.
Standard Analysis
The standards where analyzed on the Shimadzu TOC-V*W. The instrument parameters
are shown in Table 5.
Table 5-Parameters
Analysis NPOC
Injection Volume 3000 µL
Spare Time 2.00 minutes
Sparge gas flow 200 mL / min.
Acid added 3.0 %
Injections 3
Max injections 5
Carrier gas flow 200 mL / min.
Standard Results
Table 5-Results
Standard Mean Area Counts
rw 5.446
rs 78.50
rss 79.51
System Suitability
%R = [(rss-rw) / (rs-rw)] * 100 (equation 1)
%R = [(79.51-5.446) / (78.50-5.446)] * 100 = 101.4 % (equation 3)
Conclusion
According to the requirements outlined by USP, the Shimadzu TOC-V*W is suitable for
the analysis of purified water and water for injection. The three forms of oxidation give a
%R of 101.4%; validating the instrument’s ability to accurately measure TOC in the
ranges of 0.5000 mg per liter TOC. This is combined with TOC-V*W’s low
maintenance and yearly ownership of cost $888.00.
