clinical/forensic
Applications
note
Restek Corporation • (800) 356-1688 • (814) 353-1300 •
#59339
clinical/forensic
GCAnalysisof Phenylpropanolamine inColdMedicationsUsing an
Rtx
®
-5AmineColumn
Figure 1:
The Rtx
®
-5Amine column provides excellent resolution of compounds in coldmedications.
Peak List:
1. phenylpropanolamine
2. phenylephrine
3. guaifenesin
4. pheniramine
5. phenyltoloxamine
6. chlorpheniramine
7. brompheniramine
8. dextromethorphan
9. pyrilamine
10. codeine
11. hydrocodone
Rtx
®
-5AmineColumn
30m, 0.53mm ID, 1.00µm df
(cat.# 12355)
Oven temp.:
175°C to 280°C@
10°/min. (hold 5.5min.)
Inj./det. temp.:
250°C/280°C
Carrier gas:
helium
Linear velocity:
40cm/second
Sample size:
1uL
Split vent flow:
88mL/min.
Split ratio:
20:1
Until recently, phenylpropanolaminewas an ingredient in pre-
scription and over-the-countermedications. It primarilywas used
as a nasal decongestant, but alsowas used in over-the-counter
appetite suppression preparations for weight control. However, a
study by researchers at theYaleUniversity School ofMedicine
1
reported that phenylpropanolamine could increase the risk of
hemorrhagic stroke inwomen. InNovember 2000, the Food and
DrugAdministration (FDA) issued a public health advisory
requesting that all manufacturers of products containing phenyl-
propanolamine voluntarily discontinuemanufacturing andmar-
keting them.Although the risk of stroke is very low, the FDA
determined that the seriousmedical effects associatedwith stroke
outweighed the benefits derived from phenylpropanolamine. In
addition, its use is not so important because a number of other
medications can be substituted for phenylpropanolamine, espe-
cially for treating colds and sinus congestion.
Cold and sinusmedication can be analyzed for the presence of
phenylpropanolamine using a simple extraction procedure fol-
lowed by analysis using capillary gas chromatography (GC).We
surveyed themost commonly available coldmedications, and
chose two for testing. BrandAcontained phenylpropanolamine at
a concentration of 1.25mg/mLand guaifenesin at a concentration
of 10mg/mL. BrandB contained only guaifenesin at a concentra-
tion of 20mg/mL. Eachmedicationwas supplied as a syrup.
Extractionwas performed by adding 100uLof syrup to a screw-
cap culture tube andmaking it basic by adding 1.4mLof 2.5%
ammonium hydroxide. The samplewasmixed thoroughly before
adding 3mLof extraction solvent (methylene chloride:iso-
propanol, 90:10). Each samplewasmixed by gently rocking the
tube for 5minutes. The layerswere allowed to separate and the
top aqueous layer was aspirated towaste. The bottom organic
layer was transferred to a clean glass culture tube and evaporated
to dryness under a stream of dry nitrogen at room temperature.
The extractswere reconstituted for analysiswith 100µLof
methanol.
Most of the compounds in the target list, including phenyl-
propanolamine, are basic compounds that have a pKa greater
than 8.0.After passing through the extraction protocol described
above, these compounds are in the free base form in the reconsti-
tuted extract. Free bases can exhibit tailing peak shapes and
reduced response on columns that are poorly deactivated or not
designed specifically for usewith basic compounds. Because of
its superior performance analyzing free bases, anRtx
®
-5Amine
columnwas chosen for this separation.Awide bore, thick-film
columnwas needed for increased sample capacity becausemost
of the coldmedications had analyte concentrationswell above
1mg/mL.
TheRtx
®
-5Amine column provides excellent resolution of all the
compounds commonly found inmost coldmedications (see
Figure 1
). Phenylpropanolamine (peak 1) is separated easily
from the rest of the compounds.All of the target analytes exhibit
good peak shape, evenwhen in the free base form.Additionally,
the analysis is complete in less than 15minutes, which allows for
quick turn-around ofmultiple samples.
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