Measurement of Thiamylal and Thiopental in Plasma by Electron Capture and Flame PhotometricGas-Liquid Chromatography

We describe an isothermal gas-liquid chromatographic procedure developed for measuring thiamylal and thio-pental in plasma. The unchanged drug is extracted into ethyl acetate from acidified plasma, together with an in-ternal standard. The solvent is removed, the residue methylated, aliquots, diluted with benzene, are injectedinto a 183-cm gas-liquid chromatographic column containing 3 % OV-17. Sensitivity of detection is in the nanogram to picogram range. AdditIonal Keyphrases:monitoring therapy. drug assay barbiturates Thiamylal (Surital#{174},Parke-Davis) and thiopental (Pentothal#{174},Abbott) are both drugs that are used principally as “sedative-hypnotics ” to produce sleep. They are thiobarbiturates and chemically are very similar, the only structural difference is that one con-tains an allyl group where the other contains an ethyl group. Both thiamylal and thiopental are classified as ultrashort-acting agents and are used principally to induce an anesthetic state in conjunction with nitrous oxide or other inhalation anesthetics. Although deep sleep is of short duration, sedative effects persist for hours. Thus, it is desirable to accurately monitor the concentrations of barbiturates in the blood of patients during and after anesthesia. Several procedures have been published for detecting and measuring barbiturates in biological fluids: spec-trophotometric (1, 2), spectrofluorometric (3), or gas-chromatographic (4-8). However, virtually all of these procedures are intended for toxicological screens or autopsies and do not provide the sensitivity we sought. In the most sensitive method available for either thi-amylal or thiopental, the minimum detectable amount is 10 ng; its technique is alkali flame-ionization detecto