A novel gas chromatography (GC) method has been developed to accurately quantitate sodium dodecyl sulfate (SDS) in aqueous biochemical samples. This method is based on the quantitative conversion of SDS to 1-dodecanol in the GC injection port at elevated temperature, and the thermal degradation product 1-dodecanol was analyzed to determine SDS concentration. It was found that the addition of guanidinium chloride (GnHCl) to SDS samples (via direct dilution with GnHCl/MeOH solution) is necessary to ensure accurate quantitation. The presence of GnHCl enables quantitative conversion of SDS to 1-dodecanol, improves sensitivity, and virtually eliminates interference from proteins and other chemicals commonly present in biochemical samples. The method features direct analysis of diluted SDS samples, is free from interference, and is capable of quantifying less than 1 ng SDS in biochemical samples. It is also suitable for samples with limited volume, with as little as 1 microl sample being sufficient for quantitation.