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lyzer. We also studied the effect of intravenouslyadministered dipyrone in 14 patients. Dipyrone interfered significantly (P <0.05) in the determinationof CK, LD, uric acid,
triglycerides, and cholesterol with both instruments, and
creatinine only with the Ektachem analyzer. Using highperformance liquidchromatography (HPLC), we measured
concentrations of dipyrone in the serum of patients who
had received the drug and observed a negative correlation
between the concentrations of dipyrone in the blood and
the percentage of each analyte concentration.
Indexing Terms: analytical error
drug y
multilayer
film
analysis
Dipyrone
(noramidopyrine
methanesulfonate)
is an
effective analgesic, antipyretic, and antiinflammatory
drug. The pharxnacokinetics
of dipyrone after oral administration
is well documented (1,2) but the pharmacokinetics after an intravenous dose of this drug has not
been described. In spite of its recognized undesirable
effect (agranulocytosis)
(3), dipyrone is one of the most
widely used analgesic drugs in our hospital.
We found that creatinine
was undetectable
when
patients serum samples were measured by an enzymatic method (4, 5) in the Kodak Ektachem 700 analyzer; when measured by a kinetic Jaffe method (6) in a
Hitachi
747 analyzer, the same samples showed the
presence of creatinine.
After examining the medical
history of the patients, we found that all of them had
received an intravenous
injection of 2 g of dipyrone
before blood collection.
We therefore studied in vitro the effect of dipyrone on
the analytical
determination of creatinine
and several
other analytes. We then studied the effect on the analytical results of administering
dipyrone to patients
before withdrawing
blood samples.
We also measured the concentrations of dipyrone in
the blood of these patients by HPLC. The procedures
of our
4Nonstandard abbreviati
. CK, creatine
kinase; LD, lactate
dehydrogenase; AST,aspartate aminotransferase; ALT, alanine aminotransferase; BUN, urea nitrogen; GGT,L-y.glutamyltransferase.
14 patients
from the
(amoIIL)
Kodak Ektacheai
HitachI
747
Nointerference
Creatinine
Uric acid
Triglycerides
22
44
44
22
4.4
Cholesterol
44
44
44
44
89
89
89
89
1423
1423
CK
AST
ALT
BUN
LD
Final concentration/original
concentration/original* 100
Final
100
100
100
CK
80
It
60\
KODAK
40
20
HIT*C141747
&
KODAX
Dlpyroneconcentration
(pmol/L)
DipyroneconcentratIon(pmoIIL)
Finalconcentration/original
100
Finalconcentration/original
100
AST
80
ALT
40
2:
500
BUN
::
60
20
Finalconcentration/origInal
* 100
Dipyrone
concentration
(pmol/L)
Dlpyroneconcentration
(pmoi/L)
Dipyroneconcentration
(pmol/L)
Fig. 1. Effect of differentconcentrationsof dipyroneon the measurementof CK, LD, AST, ALT, and BUN
1034 CUNICAL CHEMISTRY, Vol. 39, No.6, 1993
FinalconcentratIon/origInal
* 100
TRIGLYCERIDES
80
60
40
20-
\..
20
HITACHI 747
500
1000
Dipyrone
1500
2000
concentration
2500
3000
HITACHI 747
500
Final concentration/original
1000 1500
2000
2500
3000
Dipyroneconcentration(pmol/L)
(pmol/L)
* 100
Finalconcentration/original
* 100
1u9------
CHOLESTEROL
601-
CREATININE
HITACHI 747
4O\
40
KODAK
KODAK
2:!
20
500
1000
Dipyrone
1500
2000
concentration
2500
3000
500
1000
1500 2000
2500
3000
Dipyroneconcentration(pmoi/L)
(pmol/L)
10
30
60
120
180
84.3
0.001
Mean
SD
Uric acid
0.01
Mean
SD
W
0.01
Mean
SD
Triglycerides 0.001
Mean
SD
Cholesterol
Mean
SD
0.001
Mean
SD
Creatlnine
90.7
83.6
6.2
Anolyta
CK
Mean
SD
Uric acid
Mean
SD
0.001
LD
0.01
89.8
92.5
94.2
94.2
94.6
Mean
5.1
5.4
5.9
6.1
6.8
11.8
SD
30
60
120
180
0.001
45.8 62.2 68.2
10.0
SD
Cholesterol 0.001
88.4
10
Mean
4.5
90.4
Mean
SD
Triglycerides 0.001
84.9
13.0
10.1
77.8
6.0
83.0
7.4
85.6
7.2
87.1
9.2
91.1
93.4
94.8
95.1
94.2
94.0
6.7
5.3
5.1
4.7
4.7
5.5
9.2
0.01
81.7 84.0 87.0 90.1 93.4 97.3 96.3
13.0 10.0 9.8 7.3 6.9 7.9 10.1
Discussion
In the studies in vitro, the results from the MannWhitney
U-test were consistent with the presence of
significant
negative interference
(P <0.05) by clipyrone
for the analytes listed in Table 1. The minimum
concentrations of dipyrone producing interference ranged from
22 to 1423 moI/L,
depending on the serum analyte
being measured.
No interference was observed for the measurement of
phosphate, GGT, total protein, sodium, potassium, or chloride in either instrument, and no interference was observed for creatimne in the Hitachi 747.
In the in vivo studies we found significant differences
calcium,
1035
Dlpyrone(pmor/L)
Dlpyrone (pmol/L)
Time, mm
Kodak Ektachem
Creatlnekinase
Uricacld
LD
>180
>180
60
60
Triglycerides
Cholesterol
>180
60
Creatinlne
HItachi 747
Creatinekinase
Uric acid
>180
>180
60
120
>180
LD
Triglycerides
Cholesterol
10
30 60
120180
0-
Time (mm)
10 30 60120180
Time (mm)
centrations
centrations
p
Kodak Ektachem
Creatlnine
Creatine kinase
Uric acid
LD
Triglycerides
Cholesterol
HItachi 747
Creatine klnase
Uric acid
LD
Triglycerides
Cholesterol
67
35
82
82
81
81
-0.48
<o.oi
-0.32
<0.05
<0.01
<0.05
<0.01
<o.oi
-0.85
-0.22
-v.86
-0.39
14
0.41
82
0.80
82
82
-0.24
-0.50
82
-0.20
NS
<0.01
<0.05
<0.01
NS
______
1036
No.6,1993
of analyte con-
in the Ektachem
analyzer.
Because dipyrone
1986;343:470-5.