Comparative chemical analyses of drug samples: general approach and application to heroin.

The methodology used for the comparative chemical analyses of illicit drug seizures, and its application to a heroin comparison case, is described. The illicit drug sample is subjected to a three-step procedure. The first is the qualitative and quantitative analysis of each sample, i.e. identification and quantitation of major and minor constituents. The second is the analysis of trace level impurities contained in each sample, after isolation from the drug matrix. The last step is the isotopic analysis of each sample, i.e. the determination of the isotopic enrichment of the major constituents. That analytical procedure, applied to heroin, allowed the determination of common batch samples with a high degree of certainty.

Quantitation of trihexyphenidyl from plasma using a mass-selective detector and electron-impact ionization.

A method is described for the measurement of plasma concentrations of trihexyphenidyl, an anti-parkinsonian drug. The drug was extracted from human plasma samples. Then, gas chromatography-mass spectrometry with electron-impact ionization and selected-ion monitoring allowed the specific quantitation of trihexyphenidyl, with bupivacaine used as an internal standard. Linear calibration curves were obtained in the concentration range 5-100 ng/ml. Precision and accuracy were found acceptable for quantitation during pharmacokinetic trials of the drug. This method has been successfully applied to bioavailability studies after Parkinane and Artane administration to humans.

Determination of sodium diethyldithiocarbamate (Imuthiol) and its S-methyl metabolite by gas chromatography-mass spectrometry. Use of deuteromethyl iodide derivatization.

A gas-chromatographic-mass spectrometric method is described to measure the plasma concentration of sodium diethyldithiocarbamate (ditiocarb sodium, DEDTC-Na), the active ingredient of Imuthiol, a drug found to be active in the opportunistic infections occurring in AIDS, and its S-methyl metabolite. Plasma samples are treated with deuteromethyl iodide and DEDTC-Na is transformed into its deuteromethyl ester, which is then co-extracted with the S-methyl metabolite. Gas chromatography-mass spectrometry and selected-ion monitoring allow the specific determination of both compounds. Linear calibration curves were obtained up to 4000 ng/ml. This method has been successfully applied for pharmacokinetic studies after Imuthiol and disulfiram, the dimer of DEDTC, were administered to humans.