药品质量控制中现代分析方法和技术.pptVIP

* Neutral loss scan mode is unique in that both Q1 and Q3 scan simultaneously. However, they do not transmit ions of the same m/z at the same time; rather, Q1 passes ions that are higher in m/z than Q3 at a given time. The difference in m/z equates to a neutral loss, which can be recorded as a neutral loss spectrum. This scan mode is useful for identifying drug metabolites, such as glucuronide conjugates (i.e., addition of a sugar group to a drug molecule). In the case of a glucuronidated drug, Q1 would pass ions with a m/z of (M + 176)+ while at the same time Q3 passes ions of m/z of (M)+, since the glucuronide would be lost during fragmentation in Q2. * Since buspirone fragments to generate a m/z 265 ion (see “Product Ion Spectrum of Buspirone” slide above), the corresponding neutral loss is 121 (m/z 386 – m/z 265). Setting the TSQ Quantum to neutral loss mode for 121, there are several metabolites that are identified. The peak at 13.92 minutes yielded a neutral loss spectrum (top right) where the base peak ion is m/z 402. Since this is 16 daltons higher than the unmodified buspirone (15.50 min), this compound also corresponds to a hydroxylated metabolite. * This is the scan mode mainly used for quantitative LC/MS/MS experiments on a triple quadrupole mass spectrometer. This is due to the high duty cycle of this scan mode (nearly 100%), which yields high sensitivity, and the high selectivity of SRM, which only transmits ions of a specific parent m/z and product m/z. * This slide demonstrates the importance of selectivity afforded the triple quad using SRM. An analyte, astemizole, spiked into rat plasma at a concentration of 1.5 ng/mL was analyzed using SRM and is easily detected (middle chromatogram). However, the same sample analyzed in SIM mode, which only measures a parent m/z, could not be observed due to the presence of high chemical background at the same m/z. This is the main reason triple quads are favored over single quads, which can only opera