On-site quantitation of morphine in urine by fast derivatization and miniature mass spectrometry analysis

Analysis of drugs in urine is particularly useful for screening of public safety issues, monitoring of medicine appliance and detection of drugs of abuse. Tandem mass spectrometry (MS/MS) of morphine usually produces clusters of fragments, hindering accurate quantitation of morphine in biological samples by fast sampling and direct MS/MS method. In this work, we developed a method that enabled determination and quantitation of morphine in urine in 3 min. It consisted of a simple extraction process, a fast dansyl-derivatization process, and direct analysis by a miniature mass spectrometer. MS/MS of derivatized morphine produced a highly abundant product at m/z 285 in positive ion mode, significantly enhancing the sensitivity by more than 10 times. Quantitation of morphine in urine was achieved by in-trap collision-induced dissociation on the miniature mass spectrometer, with the limit of detection of 50 ng/mL and the limit of quantitation of 100 ng/mL. The performance of the method was also evaluated with a standard liquid chromatography-MS method, showing comparable quantitative accuracy. Finally, the method has applied into quantitation of morphine in real urine samples from individuals suspected to have used opioids.

In this work, we developed a miniature MS method for fast and onsite determination and quantitation of morphine in urine. It consisted of a simple extraction process, a fast dansyl-derivatization process, and direct analysis by a newly developed miniature mass spectrometer. The whole procedures were optimized and evaluated in urine samples, showing good quantitative performance for the analysis of morphine in 3 min. The method was also compared comprehensively with the standard LC MS method for the analysis of real urine samples, showing comparable performance in quantitative accuracy and reproducibility. With minor modifications, the fast dansyl-derivatization method should be applicable to drugs of abuse with phenolic hydroxyl groups, which can improve the sensitivity of MS analysis of drugs such as morphine derivatives, tetrahydrocannabinol and propofol. In combination of simple sample preparation procedures, fast analysis process and the use of miniature mass spectrometer, this method is promising to be used for accurate quantitation of morphine for in-field or on-site applications.