12
New
Quantitation Technique for USP <467>
(External Standard)
This technique uses a separate sample
(standard) that has the compounds of interest
at known concentrations in the same matrix.
This technique is advantageous if various
samples are being analyzed, and all
compounds of interest can be assayed using
a single set external standards.
These conditions (PEAuto SYSGC andHS 40 headspace autosampler), combined
with unique columns (Rtx
®
-BAC1 andRtx
®
-BAC2), provided excellent accuracy
and precision in the analysis of blood alcohol with complete resolution in less than 3
minutes. Calibration curveswere constructed using concentrations ranging from
0.01% to 0.5% ethanol. Correlation coefficients above 0.999were easily obtained
for all compounds. Response factor repeatabilitywas less than +1% standard
deviationwhile analyzing six samples at a concentration of 0.2% ethanol. Based on
our experimentation, a system detection limit of 0.001% ethanol should be achiev-
ablewhilemaintaining aminimum signal-to-noise ratio of 10. Formore informa-
tion on this analysis request, request cat.# 59548.
USP<467>
A new test for the gas chromatographic (GC) analysis of OrganicVolatile Impurities
(OVI) in pharmaceutical productswas published in theThird Supplement to theUS
Pharmacopoeia (USP) XXII-NFXVII, which became effectiveNovember 15, 1990.
Since its original appearance in theUSP, this
testing protocol has undergonemany revisions
and additions.
1-6
Themost recent of whichwas
published asUSP 24, effective January 1, 2000.
7
The biggest changewas to the limit test concen-
trations, which nowmatch the European Pharma-
copoeia (EP) concentrations and the ICH
guidelines for the fiveUSP<467>-regulated
solvents.
8, 9
USP issued an in-process revision
announcing that the limit test for
benzene is not required unless a specific
limit for benzene is included in the
individual drugmonograph.
10
The
revisionwas needed becauseMethods I
andVwere unable to detect benzene at
2ppm. Currently,Method IV is the only
method that detects benzene at 2ppm. It
is anticipated that USPwill makemore
revisions to benzene detection limits
during 2000.
USP also has clarified that a 5m phenyl-
methyl guard column is not needed for
theMethod IV, headspace analysis.
10
Figure 13
shows an analysis using
Method IV at the revised concentrations, themethod-specified sample preparation
procedure, aG43 analytical column, and no guard column.
USPmade changes in 1997 to overcome the difficulties resulting from unregulated
solvents coelutingwith regulated solvents, and thereby causing over-representation
of their concentrations usingGC/flame ionization detection (FID)methods.
11
GC/
mass spectrometry (MS) or a second, validated column having a different stationary
phasemay be used to confirm the presence of the coeluting unregulated solvent and
report the correct concentration of regulated solvent. Formore information on this
analysis request, request cat.# 59577A.
benzene
2ppm
chloroform
60ppm
1,4-dioxane
380ppm
methylene chloride 600ppm
trichloroethene
80ppm
Limit Test Concentrations
forUSP<467>
Method IV - StaticHeadspace
6% cyanopropylphenyl/94%
dimethylpolysiloxane (G43)
30m, 0.53mm ID, 3.0µm
(Rtx
®
-G43 column, cat.# 16085-126)
Method forCoatedTablets -
Static Headspace
0.2% polyethylene glycol, MW 1500 (G39)
on graphitized carbon (S7)
(0.2%Carbowax
®
1500 on 80/100
CarboBlack
™
C packed column, cat. # 80122)
Table IV
OrganicVolatile Impurities (OVI)
methods and corresponding
chromatographic systems.
