Gas-liquid chromatography of submicrogram amounts of drugs. V. Preparation of low-activity packed columns and their application to the toxicological analysis of underivatized polar drugs in the low nanogram range.

When diatomaceous earth and glass columns are acylated prior to coating with a silicone liquid phase, then subjected to heat treatment in an atmosphere of nitrogen, gas chromatographic columns can be prepared that show a marked reduction in adsorption. These columns can be used with a nitrogen-specific detector to chromatograph unmodified polar compounds such as morphine and cyclobarbital in nanogram amounts. Virtually no alteration of peak shape and no variation of retention time are observed over the range 10(-6)-10(-9) g of polar drugs. This represents, for these polar drugs, an "improvement" in chromatographic capability of the order of about 1000-fold in comparison with the best conventional commercial columns. Application to toxicological analysis of morphine in urine is described.