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2008 vol. 2
Clinical/Forensics/Toxicology
Assure LC/MS/MS System Performance
for Drug Analyses
Using a System Suitability Test Mix
By Kristi Sellers, Clinical/Forensic Innovations Chemist and Houssain El Aribi, Ph.D., LC/MS Product Specialist, MDS Sciex
Sample throughput is a critical issue in drug toxicology, and it can be adverse-
ly affected by inferior system performance. Poor system performance can
produce unreliable data, increase downtime, and necessitate sample reanaly-
sis, which ultimately decreases sample throughput. To ensure that your
LC/MS/MS system is running properly, a system suitability mix should be
analyzed on a regular basis before case samples are analyzed.
Restek and Applied Biosystems have developed a system suitability mix
specifically for drug testing that contains compounds covering a wide range
of molecular weights, polarities, and retention times (Table I). This standards
mix is designed to verify system performance and identify system problems.
Figure 1 shows a representative chromatogram (+MRM transitions) of this
suitability mix analyzed on an Applied Biosystems API 3200™ LC/MS/MS
system. This simple test evaluates the entire analytical system, including the
autosampler, column, HPLC pumps, and mass spectrometer. The data is
automatically compared to expected results by Applied Biosystem’s Cliquid®
Drug Screen & Quant Software to identify system problems.
• Increase sample throughput and data quality with easy, reliable verification of LC/MS/MS performance.
• Extensively documented standard preparation assures accurate, consistent solutions.
• Method included in Cliquid® Drug Screen & Quant Software—automatically generates test reports.
Figure 1
Increase sample throughput by verifying system readiness with a drug standard system suitability mix.
(MRM transitions)
Sample:
system suitability mix
Inj.:
30µL
Conc.:
amiodarone
10µg/mL
amphetamine
10
caffeine
10
codeine
10
diazepam
10
doxepine
10
haloperidol
1
morphine
10
Sample diluent: methanol
LC_PH0468
caffeine
morphine
codeine
amphetamine
diazepam
doxepine
haloperidol
amiodarone
Column:
Allure
®
PFP Propyl
Cat.#:
9169552
Dimensions:
50mm x 2.1mm
Particle size:
5µm
Pore size:
60Å
Conditions:
Mobile phase:
A: 0.2% formic acid and 2mM ammonium
formate in water
B: 0.2% formic acid and 2mM ammonium
formate in acetonitrile
Time (min.):
Flow (mL/min.) %B
0.0
0.5
10
10.00
1.0
90
15.00
1.0
90
15.50
0.5
10
17.50
0.5
10
Flow:
see gradient table
Temp.:
40°C
Det.:
Applied Biosystems/API 3200™
LC/MS/MS system
Ion source:
electrospray, positive
Ion spray voltage: 4000
Gas 1:
40psi
Gas 2:
70psi
Source Temp.:
500°C
Table I
Mix components vary in chemical
properties, providing a rigorous system
performance test.
Mass Spectrometer Conditions:
Analyte
MW RT (min)
Q1
Q3
Amiodarone
645
12.30 646.0
58.0
Amphetamine
135
4.21 136.1
91.1
Caffeine
194
1.72 195.1 122.9
Codeine
299
3.47 300.2 165.2
Diazepam
284
5.25 285.1 193.2
Doxepin
279
8.72 280.2 107.1
Haloperidol
375
9.08 376.1 123.0
Morphine
285
2.24 286.1 165.1