Validiflon of assay methods for chlorproguanil., and chlorcycloguanil and its application to pharmacokinetics studies
| dc.contributor.author | Sulaiman, Maryam (Hj.) | |
| dc.date.accessioned | 2015-07-30T03:07:12Z | |
| dc.date.available | 2015-07-30T03:07:12Z | |
| dc.date.issued | 1996 | |
| dc.description.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. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/944 | |
| dc.language.iso | en | en_US |
| dc.subject | Chlorproguanil | en_US |
| dc.subject | Pharmacokinetics | en_US |
| dc.title | Validiflon of assay methods for chlorproguanil., and chlorcycloguanil and its application to pharmacokinetics studies | en_US |
| dc.type | Thesis | en_US |
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