NAVELBINE: Fast Detection in Urine Sample with

Transcription

NAVELBINE: Fast Detection in Urine Sample with
OraChrom, Inc.
The Vanguard of Liquid Chromatography.
10-B Henshaw Street Woburn, MA 01801 USA
Phone (781) 932 0151
Fax
(781) 932 0787
E-mail: [email protected] www.orachrom.com
APPLICATION NOTE
Navelbine: Fast Detection in Urine Sample with STYROS 2R/XH.
Navelbine is a semi-synthetic vinca alkaloid with antitumor
activity. It is the ditartrate salt of Vinorelbine.
CH3
N
Navelbine
H
The chromatograms show the speed and accuracy with which the
treating physician can access this crucial information to make an
informed judgment during treatment.
At present, the only short term guide is the patient’s symptoms
during the following days. The long term side effects as well as
the cumulative ones are less clear. Often times the symptoms are
irreversible and the treatment needs to be discontinued.
Table 1. Operating parameters for the chromatograms.
Mobile Phase
N
OCH3
CH3
CH3O
H
O
N
+ 2 COOH-CHOHCHOH-COOH
H
O
H3C
OH
O
CH3
1.071
0.806
100
The metabolisms of vinca alkaloids are known to be mediated by
hepatic cytochrome P450 isoenzymes in the CYP3A subfamily. It
is therefore important to consider any hepatic dysfunction as well
as any potent metabolic inhibitor when administering the drug to
these patients.
The metabolites of Vinorelbine in excess doses have been
detected in the blood, plasma and urine. However, in therapeutic
doses of up to 30 mg/m2, hardly any metabolite can be detected
either in the blood or in the urine.
The present application shows how one can effectively gauge the
excess drug after its intravenous administration during a short
chromatographic run.
Judging by the patient’s blood count, Vinorelbine’s effect can be
seen for up to 14 days. However, no detectable peek can be
recorded after 12 hrs during chromatographic run using urine
samples.
1
2
3.402
3
4
Min
T= 1 hr
3.564
Chromatogram 1
STYROS 2R/XH
4.6 X 50 mm
Samples of urine taken
after injection of
Navelbine.
T= 1 hr
Navelbine
3.396
3.396
3.564
2.785
3.137
2.388
2.577
1.722
2.016
% Buffer B
0
T= 6 hrs
3.564
T= 12 hrs
T= 8 days
3.396
3.137
2.577
2.785
2.016
2.388
Navelbine
T= 6 hr
T= 12 hrs
Flow rate
Gradient
Temperature
Detection
Injection volume
Sample:
O CH3
The clinical pharmacology suggests that the drug’s action results
in its interference with microtubule assembly.
Navelbine concentration in plasma rapidly decreases after
intravenous injection. This represents the peripheral distribution
to the point of saturation. The excess drug is flushed out in urine
within an hour.
Using urine samples from the patient one can monitor excess
drug and therefore adjust the injected amount to prevent any
unnecessary and rather harmful overdose.
0
Agilent 1100
STYROS 2R/XH 4.6 X 50 mm
A: 0.075% TFA in H2O
B: 0.075% TFA in ACN:H2O (95:5)
1 ml/min (360 cm/hr)
5% B for 0.3 min., to 100% B in 4 min.
37C
252 nm
25 l
As indicated.
HPLC System.
Column
N
H O
3.35
2.0
3.0
3.4
3.45
3.5
3.55
3.6
3.65
Min
Min
AN071904-35