Mass fragmentography of morphine: relationship between brain levels and analgesic activity.

Morphine levels in rat brain were measured by the multiple ion detection method (mass fragmentography), using a computer-controlled gas chromatograph-mass spectrometer, and were correlated with the analgesic activity of the narcotic at intervals up to 6 hours after the injection. Morphine levels in brain reached a peak of 346 ng/g of tissue wet weight 30 minutes after the subcutaneous injection of 10 mg/kg of morphine sulfate and then declined rapidly over the next 3 hours. Between 3 and 6 hours after the injection of morphine, the brain concentration decreased slightly but was still readily detectable at 6 hours after injection. An excellent correlation (r = 0.923) was found between the concentration of morphine in brain and analgesic activity, as measured by the hot plate method. The multiple ion detection method for the measurement of morphine appears to meet all of the criteria necessary for any drug assay: sensitivity, specificity and ease of analysis.