Analysis of paracetamol using solid-phase extraction, deuterated internal standards, and gas chromatography-mass spectrometry.

A rapid method for determining paracetamol (acetaminophen) in whole blood and liver tissue samples is described. Blank plus single-point calibration gives reliable quantitation at therapeutic and higher concentrations. Whole blood and liver tissue samples containing a deuterated internal standard were extracted using Bond Elut Certify columns. Butyl derivatives were formed using n-iodobutane and tetramethyl ammonium hydroxide under mild conditions and were extracted into ethyl acetate as a cleanup step. Recovery was better than 90%, and sample preparation time was less than 2 h. Gas chromatograph run time was less than 20 min. SIM of two ion pairs formed by electron impact ionization resulted in intraday coefficients of variation (CV) less than 3.03% (7.48% in liver) and interday CVs less than 8.93% (for midtherapeutic concentrations in whole blood). Linearity was observed from subtherapeutic to high, fatal levels. This method has been applied to forensic cases and has significantly reduced analytical time while improving casework quality. Results of a case study involving paracetamol are given.

Analysis of six anticonvulsant drugs using solid-phase extraction, deuterated internal standards, and gas chromatography-mass spectrometry.

A rapid method for simultaneously determining the anticonvulsant drugs carbamazepine, ethosuximide, phenobarbitone, phenytoin, primidone, and valproic acid is described. Blank plus single-point calibration gives reliable quantitation from therapeutic to high fatal concentrations, except for ethosuximide, for which it gives semiquantitative results. Whole blood and liver tissue samples containing deuterated internal standards were extracted using Bond Elut Certify columns. Butyl derivatives were formed using n-iodobutane and TMAH under mild conditions and were extracted into ethyl acetate as a cleanup step. Recoveries were greater than 50%, except for valproic acid (42%). Sample preparation time was less than 2 h, and the GC run time was less than 20 min per injection. At least two ion pairs formed by electron impact ionization were monitored for each drug. Intraday CVs were less than 6.28% (4.20%) and interday CVs less than 14.1% (for midtherapeutic concentrations in blood [liver], except for ethosuximide). Linearity was observed from subtherapeutic to high fatal levels for all drugs. This method has been applied to forensic cases and has significantly reduced analytical time while improving case-work quality. Results of a case study involving anticonvulsant drugs are given.

Bicarbonate as an interference in B. stearothermophilus assays.

The screening analysis of antibiotic residues in meat products is readily accomplished by a suite of bacterial inhibition assays. Inhibition of B. stearothermophilus is a standard assay noted for its sensitivity to penicillins. In New Zealand, a test kidney from slaughtered animals is accompanied by a urine sample. Generally, penicillins and tetracyclines are both richer in the urine sample, which is applied directly to wells cut in bacterially seeded agar plates. An interference in the assay for B. stearothermophilus has been traced to excessive amounts of bicarbonate in the urine. It is the bicarbonate, not the pH nor the ionic strength that causes the problem. Removal of the bicarbonate was by mild acetic acid treatment to pH 5.5 and vortex mixing to de-gas carbon dioxide. This resulted in complete eradication of the interference without affecting the ability to detect penicillin. The pH change was readily monitored by the indicator bromcresol purple and no complex equipment was needed.

Quantitative analysis of alprazolam and triazolam in hemolysed whole blood and liver digest by GC/MS/NICI with deuterated internal standards.

This report describes sensitive and specific methods for the quantitation of alprazolam and triazolam in hemolysed whole blood and liver tissue. Samples of blood and enzyme-digested liver are extracted without pH adjustment with n-butyl chloride, after addition of deuterated internal standards and urea. The evaporated extracts are reconstituted in acetonitrile for analysis by gas chromatography/mass spectrometry/negative ion chemical ionization (GC/MS/NICI). Fatty extracts may be cleaned up by partitioning between pentane and acetonitrile. Two ion pairs are monitored for each drug. Within-day coefficients of variation in the range 10-50 micrograms/L for blood are approximately 5%. Between-day coefficients of variation are less than 10%. The limit of quantitation (based on analysis of 0.2-mL blood samples) is 0.5 microgram/L for triazolam and 4 micrograms/L for alprazolam.

Anatomic considerations of pin placement in the proximal tibia and its relationship to the peroneal nerve.

Peroneal nerve impalement is a recognized complication of percutaneous placement of wires, which is gaining increased usage with the application of the techniques of Ilizarov, Monticelli, and Spinelli. Dissections of the peroneal nerve in the proximal tibia were performed in ten anatomic specimens (20 legs) to define (1) its relationship to palpable landmarks, (2) distribution of major branches to the musculature, and (3) safe zones of placement of percutaneous wires in the proximal tibia. The anterior recurrent tibial nerve was frequently in an area of risk where it courses proximally in the anterior compartment. A safe zone is located anterior to the palpable portion of the fibular head and up to 2 cm distal to the tip of the fibular head.

Salivary THC following cannabis smoking correlates with subjective intoxication and heart rate.

A cannabis smoking trial was conducted using paid volunteers. Subjective intoxication, measured using a visual analogue scale, was compared with heart rate and with salivary delta-9-tetrahydrocannabinol (THC) levels at various times after smoking a cigarette containing 11 mg THC. Subjective intoxication and heart rate elevation were significantly correlated with the log of salivary THC. Salivary THC levels are a sensitive index of recent cannabis smoking, and appear more closely linked with the effects of intoxication than do either blood or urine cannabinoid levels.