High-performance liquid chromatography of proguanil, cycloguanil and 4-chlorophenylbiguanide using hydrophobic pairing ion and its application to serum assay

Moody, R.R.; Selkirk, A.B.; Taylor, R.B.

doi:10.1016/s0378-4347(00)81485-1

Cited by 26 publications

(6 citation statements)

References 13 publications

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“…These methods however lacked both sensitivity and selectivity. Recently plasma and urinary concentrations of proguanil and cycloguanil have been determined by high performance liquid chromatography (Moody et al, 1980;Edstein, 1986;Kelly & Fletcher, 1986). Watkins et al (1987) used a bioassay technique to determine the plasma concentrations of cycloguanil after a single dose of proguanil (200 mg).…”

Section: Introductionmentioning

confidence: 99%

Inter‐subject variability in the metabolism of proguanil to the active metabolite cycloguanil in man.

Ward

Watkins

Mberu

et al. 1989

Brit J Clinical Pharma

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1. The metabolism of proguanil to the active metabolite cycloguanil has been evaluated in 135 British Troops and 26 Kenyan schoolchildren. 2. Large inter‐subject variability was observed in both plasma and urinary concentrations of proguanil and cycloguanil after standard doses of drug. 3. Based on the ratio of proguanil to cycloguanil (P/C) in urine the British troops formed a non‐normal distribution. 90% of the population formed a discrete distribution with P/C ranging from 0.5 to 9.0 while the remaining 10% were scattered throughout the distribution to an extreme value of 39. A similar pattern of variability was observed using P/C from a 6 h plasma sample. 4. This variability was due to differences in the ability of individuals to metabolise proguanil to cycloguanil. 5. Thirteen schoolchildren who had experienced malaria during prophylaxis with proguanil and thirteen matched controls each received proguanil (100 mg). We could not discriminate between the two groups based on P/C ratio in either a 6 h plasma or 0‐6 h urine sample.

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Section: Introductionmentioning

confidence: 99%

Inter‐subject variability in the metabolism of proguanil to the active metabolite cycloguanil in man.

Ward

Watkins

Mberu

et al. 1989

Brit J Clinical Pharma

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“…Recently several specific h.p.l.c. assay methods have been described (Moody et al, 1980;Edstein, 1986;Kelly & Fletcher, 1986) and some preliminary plasma drug concentration data have been reported, but these have been insufficient for adequate pharmacokinetic analysis. We have now refined the sensitivity and specificity of the earlier h.p.l.c.…”

Section: Introductionmentioning

confidence: 99%

Single dose pharmacokinetics of proguanil and its metabolites in healthy subjects.

Wattanagoon

Taylor

Moody

et al. 1987

Brit J Clinical Pharma

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Hospital, Headington, Oxford OX3 9DU 1 Plasma and whole blood concentrations of proguanil and its two major metabolites cycloguanil (CG) and 4-chlorophenylbiguanide (CPB) were measured by a sensitive h.p.l.c. technique in nine healthy adult male volunteers after a single oral dose of proguanil 200 mg.2 Proguanil was absorbed with a median time to peak plasma concentration of 3 h (range 2-4 h).3 Peak plasma concentrations of proguanil ranged between 150 and 220 (median 170) ng ml-' compared with 12 to 69 (median 41) ng ml-' for the active antimalarial metabolite CG, and 3 to 16 (median 11) ng ml-' for CPB. Peak (mean ± s.d.) plasma CG concentrations occurred 5.3 ± 0.9 h and peak CPB concentrations occurred 6.3 ± 1.4 h after oral administration of proguanil. 4 Whole blood concentrations of proguanil were approximately five times higher, and whole blood CPB concentrations were four times higher than corresponding plasma values, whereas plasma and whole blood concentrations of CG were similar. 5 A triexponential function was fitted to these data; mean (± s.d.) values for the AUC were 3046 ± 313 ng ml-' h for proguanil, 679 ± 372 ng ml-' h for CG and 257 ± 155 ng ml-1 h for CPB. 6 Plasma and whole blood concentrations of proguanil and its metabolites declined in parallel with terminal elimination half-lives estimated as 16.1 ± 2.9 h and 15.7 + 2.4 h, respectively. Mean residence times in plasma and whole blood were estimated as 21.2 ± 4.9 and 19.3 ± 2.4 h.

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“…The pharmacokinetic characteristics of a drug have been implicated in the mechanism through which parasites develop resistance to it (Moody et al, 1982). The elucidation of the pharmacokinetic characteristic of proguanil is therefore necessary if its continued use and potency is not to be forfeited.…”

Section: Introductionmentioning

confidence: 99%

“…There are however a few chromatographic methods with the advantage of specificity and sensitivity. The pioneering chromatographic work by Moody et al (1982) utilized reverse phase ion pairing high performance liquid chromatographic technique for the separation of proguanil and its two major metabolites cycloguanil and 4 -chloro phenyl biguanide. A detection limit of 60 ng/ml of sample volume was achieved with the method.…”

Section: Introductionmentioning

confidence: 99%

“…The modifications made to the methods described by Moody et al (1982) included the extraction procedure and a change in the ion pairing agent from sodium lauryl sulphate to pentane sulphonic acid. Kelly and Fletcher (1986) also made slight modifications to the liquid extraction procedures of Moody et al (1982) and the ion pairing agent to achieve improved sensitivity.…”

Section: Introductionmentioning

confidence: 99%

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High performance liquid chromatographic determination of proguanil after derivatisation with sodium benzoxazole-2-sulphonate

Adewuyi¹,

Olubomehin²,

Ayanniyi³

2010

Afr. J. Biotechnol.

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A simple, fast and reproducible method for the determination of proguanil using high performance liquid chromatographic with UV/Fluorescence detection is described. Proguanil was derivatised to its corresponding derivative [(N 1 -(4-chlorophenyl)-N 5 -(1 -methyl ethyl) imidocarbonimideamide-Nbenzoxazole]. The derivatisation reaction was conducted in methanol at 60°C using sodium benzoxazole-2-sulphonate under alkaline conditions. The resulting derivative was extracted with chloroform after which the extract was observed under UV lamp at 254 nm before TLC and HPLC analysis. Similarly, the derivatisation process was adapted for derivatisation of proguanil in urine sample. The reaction proceeded smoothly and rapidly. The extraction process was not cumbersome and eliminated the need for costly extraction and evaporation equipments. The resulting derivative fluorensced intensely under UV lamp. Direct HPLC analysis of the reaction mixture was found possible without interferences from excess reagent and endogeneous compounds like ammonium salts. The derivative eluted in less than seven minutes thus making the method suitable for routine use. The calibration plot was linear over the concentration range. A correlation regression of the order of 0.94 was obtained from the calibration curve which indicated a strong relationship between the instrument response and the concentration of proguanil. The discussion also summarizes the derivatisation chemistry that have not being fully explored to date but may find utility in future development of highly sensitive analytical methods for biquanide drugs.

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High-performance liquid chromatography of proguanil, cycloguanil and 4-chlorophenylbiguanide using hydrophobic pairing ion and its application to serum assay

Cited by 26 publications

References 13 publications

Inter‐subject variability in the metabolism of proguanil to the active metabolite cycloguanil in man.

Inter‐subject variability in the metabolism of proguanil to the active metabolite cycloguanil in man.

Single dose pharmacokinetics of proguanil and its metabolites in healthy subjects.

High performance liquid chromatographic determination of proguanil after derivatisation with sodium benzoxazole-2-sulphonate

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