Determining plasma morphine levels using GC-MS after solid phase extraction to monitor drug levels in the postoperative period.
OBJECTIVE
To implement a selective and sensitive analytical method to quantify morphine in small volumes of plasma by gas-liquid chromatography-mass spectrometry (GC-MS), aimed at post-operatively monitoring the drug.


METHODS
A gas-liquid chromatographic method with mass detection has been developed to determine morphine concentration in plasma after solid phase extraction. Morphine-d3 was used as an internal standard. Only 0.5 mL of plasma is required for the drug solid-phase extraction in the Bond Elut-Certify, followed by the quantification of morphine derivative by GC-MS using a linear temperature program, a capillary fused silica column, and helium as the carrier and make-up gas. The method was applied to determine morphine content in plasma samples of four patients during the postoperative period of cardiac surgery. Patient-controlled analgesia with morphine was performed by a venous catheter, and a series of venous blood samples were collected. After the oro-After the orotracheal extubation, morphine plasma levels were monitored for up to 36 hours.


RESULTS
The run time was 16 minutes because morphine and the internal standard were eluted after 8.8 minutes. The GC-MS method had 0.5 -1000 ng/mL linearity range (r(2)=0.9995), 0.1 ng/mL limit of detection, intraday and interday precision equivalent to 1.9% and 6.8%, and 0.1% and 0.8% systematic error (intraday and interday, respectively). The analytical method showed optimal absolute (98%) and relative (100.7%) recoveries. Morphine dose requirements and plasma levels are discussed.


CONCLUSIONS
The analytical gas-liquid chromatography-mass spectrometry method is selective and adequate for morphine measurements in plasma for applications in clinical studies.
School of Pharmaceutical Sciences, Universidade de São Paulo, São Paulo, SP, Brazil.
Veronica
V
Santos
Karin Jannet Vera
KJ
López
Luciana Moraes
LM
Santos
Mauricio
M
Yonamine
Maria José Carvalho
MJ
Carmona
Silvia Regina Cavani Jorge
SR
Santos
D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods*; D004355:Drug Stability; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000097:blood*; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000097:blood; D011184:Postoperative Period; D012680:Sensitivity and Specificity; D052616:Solid Phase Extraction
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D009020:Morphine