286 / 413
•
8
•
2007 vol. 2
Clinical/Forensics/Toxicology
Figure 2
A base-deactivated inlet liner provides highest mean
responses for PCP.
Figure 3
Linearity plots for all drugs, analyzed using a
base-deactivated inlet liner and an Rtx®-5 Amine column.
Figure 1
Basic compounds can react with silanol groups on glass
liner surfaces, causing poor chromatography.
Clinical and forensic toxicologists are required to
detect low levels of abused drugs in body fluids and
confirm their presence by GC/MS. Typical limits of
detection are 1-15ng/mL, depending on the sample
matrix. For basic drugs (e.g., Figure 1), selecting
the proper surface treatment for the GC inlet liner
is important, because this parameter can affect
responses. The surface of a glass inlet liner contains
active silanol groups (Si-OH) that can act as elec-
tron pair acceptors, and react with nitrogen or oxy-
gen electron pair donors in basic drug molecules
(Figure 2).
1
These reactions usually are rapid and
reversible, but they are expressed chromatographi-
cally as broad, tailing peaks and/or reduced
responses. To eliminate these acid-base reactions,
make chromatographic peaks sharp, Gaussian, and
easy to integrate, and thereby help ensure repro-
ducible and accurate responses, the -OH groups on
the glass surface must be deactivated.
We evaluated several alternatives for deactivating
inlet liners to determine the best deactivation
chemistry for the analysis of basic drugs. Standards
composed of the free base forms of the drugs
shown in Figure 1 were prepared at concentrations
of 5, 10, 25, 50, and 100 ng/mL for analysis on a
15m, 0.25mm ID, 0.25μm Rtx®-5 Amine column
(5% diphenyl/95% dimethyl polysiloxane station-
ary phase). The analysis of these drug standards
was repeated on a series of 4mm ID single goose-
neck liners that had been treated with different
deactivation techniques, as well as an untreated
liner. Three replicate analyses were performed on
each liner to determine which deactivation treat-
ment offered the highest and most consistent
response for these basic drugs.
We used these results to generate box plots that
display the range of data distribution, or variation
– an indication of the reproducibility of the per-
formance. We chose phencyclidine (PCP) and
cocaine plots to represent the nitrogen-containing
and nitrogen/oxygen-containing drugs, respective-
ly (Figure 2). The line in each box indicates the
mean response.
The data show that undeactivated liners and liners
that received intermediate polarity treatment pro-
vided poorer responses or reproducibility, com-
GC Inlet Liner Deactivations for Basic Drug Analysis
By Kristi Sellers, Clinical/Forensic Innovations Chemist, and Lydia Nolan, Innovations Chemist
• Base-deactivated inlet liners are inert to basic drugs, for greater responses.
• Inertness of Rtx®-5 Amine column is enhanced for basic compounds.
• Use this liner / column combination for the lowest %RSDs for basic drugs.
Benzphetamine
Cocaine
Alprazolam
Phencyclidine
Ketamine
Methadone
Codeine
Undeactivated
Glass Surface
Si
O Si
O Si
OH
OH
OH
5ng PCP
5ng Cocaine
Base
Deactivation
Conventional
Deactivation
Base
Deactivation
Conventional
Deactivation
Liner
ng/mL on column
Liner
PCP Area
area counts
Cocaine Area
90
80
70
60
50
145
140
135
130
125
120
2500
Benzphetamine
Ketamine
Phencyclidine
Methadone
Cocaine
Codeine
Alprazolam
2000
1500
1000
500
0
0
10
20
30
40
50
60
70
80
90
100