Validiflon of assay methods for chlorproguanil., and chlorcycloguanil and its application to pharmacokinetics studies
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Date
1996
Authors
Sulaiman, Maryam (Hj.)
Journal Title
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Abstract
Two assay methods have been developed and valjdated for the
analysis of chlorproguanil and chlorcycloguanil. The gas
chromatographic procedur~ with electron-capture detector
( GC-ECD) was developed for the analysis of chlorproguani 1
while a reverse phase liquid chromatographic procedure with
ultra-violet detector at 235nm (HPLC-UV) was developed to
assay for chlorcycloguanil alone.
The gas chromatographic procedure developed, using
proguani.l as the internal standard, gave good resolution
for proguanil and chlorproguanil. A linear response was
obtained over the rang~ 1.0 - 50.0ng. The average recovery
for, chlorproguanil was 80.8 + 5. 4%. Extraction recoveries
were linear for chlorproguanil within the range 2.0-40ng/ml
( c o e ·f f i c i en t o f c o r r: e 1 a t i o n = o . 9 9 6 ) . •r he w i t h i n - day
precision for chlorproguanil gave coefficient of variation
between 4. 9% - 7. 9% at1d day-to-day pred 1; ion \.Jas between
0.72 - 7.3%. The assay sensitivity was 0.1 ng/ml for
chlorproguanil.
In the HPLC procedure cycloguanil was used as the internal
standard. Detector linearity for chlorcycloguanil was
obta.ined over the range· J • 0 - 80 ng. The average recovery
of chlocycloguanil was found to be 99.4 + 5.6%. The
within-day coefficient of variation was between 1.8% - 6.8%
and day-to-day was 4. 5 9. 2%. The limit of assay
sensitivity by HPLC-U~ was 0.5ng/ml.
The pharmacokinetic study on healthy Malaysian volunteers
was carried out. Chlorproguanil is well tolerated an6 safe
Ln all subjects receiving 20 mg of Lapudrine tablet
administered as a single oral dose. In our study one
subject appears to absorb chlorproguanil to a limited
extent. The mean Cmax for chlorproguanil was 25 + 4 ng/ml
and the mean tmax was 3.0 ± 1.2 hour. Chlorproguanil has a
mean t 1; 2 of 37.1 + 19.5 hour and a mean plasma CL of 0.93
f 0.26 L/hr/kg. The mean Vd was 51.1 ! 38.1 L/kg while the
mean AUC 0 _ ex 365 + 101 ng hr/ml was observed.
Chlorcycloguanil was measurable in only two subjects
and the mean AUC 0_ ~ in these subjects was 147.6 ± 11.0 ng
. hr/ml. The mean Cmax and tmax for all subjects were 6.7 +
5.0 ng/ml and 5.6 ~ 3.0 hour respectively. Our study
indicates that there are slight pharrnacokinetic differences
of chlorproguanil in Malaysian volunteers as compared to
those derived in the Caucasian subjects. Factors such as
dose size weight of the subjects and genetics may
contribute to the differences in the. pharrnacokinetic
parameters of chlorproguanil in ltealthy volunteers.
Description
Keywords
Chlorproguanil , Pharmacokinetics