A high performance liquid chromatographic assay of mefloquine in saliva after a single oral dose in healthy adult Africans

对非洲健康成年人单次口服甲氟喹后唾液中的甲氟喹进行高效液相色谱测定

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作者:Grace O Gbotosho, Christian T Happi, Omowunmi Lawal, Abayomi Sijuade, Akin Sowunmi, Ayoade Oduola

Background

Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT) recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries. Efforts in this study were devoted to the development of a simple, field applicable, non-invasive method for assay of mefloquine in saliva.

Conclusion

Disposition of mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring.

Methods

A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column.

Results

Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, p < 0.001). Saliva:plasma concentrations ratio was 0.42.

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