Restek Corporation • (800) 356-1688 • (814) 353-1300 •
Figure 3
shows an analysis using USP 24 <467> Method V, a G43
analytical columnwith a phenylmethyl guard column and, once again,
a 1:10 dilution in order to obtain a detectable benzene peak.
USPmade changes in 1997 to overcome the difficulties resulting from
unregulated solvents coeluting with regulated solvents, and thereby
causing over-representation of the latter concentrations usingGC/flame
ionization detection (FID) methods.
12
GC/mass spectrometry (MS) or a
second, validated column having a different stationary phase may be
used to confirm the presence of the coeluting unregulated solvent and
report the correct concentrationof regulated solvent.
Figures 4, 5, and
6
show the different elutionorders for commonly-used pharmaceutical
processing solvents on G27, G43, and Stabilwax
®
columns. The latter
are useful secondary columns for confirmational analysis.
We will continue to review changes to pharmaceutical OVI testing.
Restek referencematerials listedonpage4of thisapplicationsnotemeet
themost recent USP updates.
Formore information regarding these
applications, please callRestek technical service at 800-356-1688or
814-353-1300, ext. 4, or your local Restek representative.
1. methylene chloride 600ppm
2. chloroform
60ppm
3. benzene*
2ppm
4. trichloroethylene
80ppm
5. 1,4-dioxane
380ppm
1. methylene chloride 600ppm
2. chloroform
60ppm
3. benzene*
2ppm
4. trichloroethylene
80ppm
5. 1,4-dioxane
380ppm
Sample Preparation:
1:10 dilution of cat.# 36007 in distilledwater (this deviation
from the 1:50 dilution in themethodwas needed to obtain a detectable benzene peak).
30m, 0.53mm ID, 3.0µmRtx
®
-G43with 5m phenylmethyl Integra-Guard
™
(cat.# 16085-126). ThermoQuest Trace 2000 Series. Uniliner
®
direct injection sleeve.
Oven temp.:
40°C (hold 20min.) to 240°C@ 35°C/min. (hold 20min.);
Inj. temp.:
140°C;
FID sensitivity:
260°C, 1 x 10
-11
AFS;
Carrier gas:
4.1psi helium@ 35°C/sec.,
Det. temp.:
260°C
References
1. M.S. Bergren andD.W. Foust, “Comments onUSPGeneral Chapter, OrganicVolatile Impurities
<467>, andAssociatedMonograph Proposals,”
Pharmacopoeial Forum
,
May/June 1991,Vol. 17, No. 3, pp. 1963-1968.
2. J.A. Krasowski, H. Dinh, T.J. O’Hanlon, R.F. Lindauer, “Comments onOrganicVolatile Impurities,
Method I, <467>,”
Pharmacopoeial Forum
,May/June 1991,Vol. 17, No. 3, pp. 1969-1972.
3. Pharmacopoeial Forum,March/April 1991,Vol. 17, No. 2, p. 1653.
4. Fifth Supplement, USP-NF, OrganicVolatile Impurities <467>, Nov. 15, 1991, pp. 2706-2708.
5. “OrganicVolatile Impurities <467>,”
Pharmacopoeial Forum
,May-June 1993,Vol. 19,
No. 3, pp. 5335-5337.
6. Pharmacopoeial Forum, September/October 1992,Vol. 18, No. 5, p. 4028.
7. USP 24/NF 19, <467>OrganicVolatile Impurities, (1877-1878).
8. “ICHHarmonizedTripartiteGuideline, Impurities: Guideline for Residual Solvents,”
The Fourth International Conference onHarmonization
, July 17, 1997.
9. European Pharmacopoeia, Supplement 1999, pp. 14-15, 208.
10. Pharmacopoeial Forum, November - December 1999,Vol. 25, Number 6, (9223 - 9224).
11. Supplement Two, USP 24/NF 19,August 1, 2000.
12. Sixth Supplement, USP-NF, OrganicVolatile Impurities <467>,May 15, 1997, pp. 3766-3768.
13. USP 25/NF 20, <467>OrganicVolatile Impurities, January 1, 2002.
4
5
4
3
2
1
2 3 4 5 6
min.
1
2
3
5
2 3 4 5 6 7 8
min.
These references are not available fromRestek.
Sample Preparation:
100µL of cat.# 36007 in 5mL distilledwater,
1g sodium sulfate in a 20mL headspace vial.
30m, 0.53mm ID, 3.0µmRtx
®
-G43 (cat.# 16085)
Oven temp.:
40°C (hold 20min.) to 240°C@ 35°C/min. (hold 20min.);
Inj. temp:
140°C, 1mm split sleeve (cat.# 20916);
Det. temp.:
260°C;
FID sensitivity:
1.25 x 10
-11
AFS;
Carrier gas:
helium, 3.5psi constant pressure, 35cm/sec. set@ 40°C;
Split ratio:
2:1; ThermoQuest HS 2000HeadspaceAutosamplerVial 80°C,
60min. shaker on.
*Testing for benzene only requiredwhen specified in the individual monograph.
*Testing for benzene only requiredwhen specified in the individual monograph.
Figure 2
Figure 3
The Rtx
®
-G43 column provides the resolution and
detection limits needed for <467>
revised limit test concentrations inUSPMethod IV.
(no guard column)
Achieve analysis of 2ppm benzene forMethodV, using
1:10 dilution and anRtx
®
-G43 column.
