The aim of present work was to optimize the experimental parameters in single drop microextraction under solution immersion (SDME) and headspace (HS-SDME) extraction modes for the determination of periodate using guaifenesine [3-(2′-methoxyphenoxy)-1,2-propane diol] and norephedrine (phenylpropanolamine) as new and alternative reagents for the Malaprade reaction. The reactions were complete within 5min resulting in the formation of 2-(2′-methoxyphenoxy)-acetaldehyde and benzaldehyde, respectively. SDME/HS-SDME of oxidation products with 2μl of anisole or 1μl of toluene, respectively, has permitted the determination of periodate at μgl −1 concentration levels. The results indicated that HS-SDME (range 0.01–10mgl −1 , r 2 =0.9990; limit of detection 1.55μgl −1 ) was more sensitive than SDME (range 0.05–50mgl −1 , r 2 =0.9984; limit of detection 3.42μgl −1 ), and was inexpensive, rapid and convenient. Tolerance of excess of iodate has permitted the application of this method in the determination of ethylene glycol in motor oil; the average recovery on spiked sample was 98.6% with R.S.D. of 4.2%.