title: Poor reproducibility of in-source collisional atmospheric pressure ionization mass spectra of toxicologically relevant drugs.
abstract: The purpose of the study was to examine the intra- and interlaboratory reproducibility of mass spectra obtained with liquid chromatography-atmospheric pressure ionization mass spectrometry (LC--API-MS) both in electrospray (ESI) and atmospheric pressure chemical ionization (APCI) modes. Toxicologically relevant drugs of different polarity were selected as test substances: morphine-6-glucuronide, 6-monoacetylmorphine, codeine, lysergic acid diethylamide, methylenedioxymethamphetamine. The study was performed in two laboratories using identical instruments and in one using a slightly different instrument. Basic instrument settings and mobile phase were identical in all laboratories. Mass spectra of drugs were taken at four collision energy voltages and using mobile phase of different composition (four concentration levels of acetonitrile and of ammonium formate buffer). The experiments demonstrated that mass spectra of given drugs, obtained in identical conditions with identical instruments, may show very different degrees of fragmentation. Mass spectra obtained with different instruments differed profoundly not only in the degree of fragmentation, but also different fragments and adducts were observed. Short-term intralaboratory reproducibility of mass spectra was satisfactory. On the other hand, the long-term experiments showed different degrees of fragmentation of APCI-generated mass spectra at nominally identical fragmentation energy. The changes in the composition of the mobile phase (concentration of organic modifier or buffer molarity) did not affect the reproducibility of fragmentation to any relevant degree. The study showed that the interlaboratory exchange and use of mass spectrum library, generated by single-quadrupole (LC--API-MS instruments, is hardly feasible at the moment, even under very carefully standardized conditions.
authors.affiliation: Institute of Forensic Medicine, Aachen University of Technology, Germany. bogusz@amsd.imib.rwth-aachen.de
authors.forename: M J
authors.initials: MJ
authors.lastname: Bogusz
authors.forename: R D
authors.initials: RD
authors.lastname: Maier
authors.forename: K D
authors.initials: KD
authors.lastname: Krüger
authors.forename: K S
authors.initials: KS
authors.lastname: Webb
authors.forename: J
authors.initials: J
authors.lastname: Romeril
authors.forename: M L
authors.initials: ML
authors.lastname: Miller
mesh_terms: D001274:Atmospheric Pressure; D006213:Hallucinogens / Q000032:analysis*; D008238:Lysergic Acid Diethylamide / Q000032:analysis; D013058:Mass Spectrometry; D009022:Morphine Derivatives / Q000032:analysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000032:analysis; D009294:Narcotics / Q000032:analysis*; D015203:Reproducibility of Results; D014116:Toxicology / Q000379:methods*
chemical_list: D006213:Hallucinogens; D009022:Morphine Derivatives; D009294:Narcotics; D008238:Lysergic Acid Diethylamide; D018817:N-Methyl-3,4-methylenedioxyamphetamine