Quantitative analysis of the relationship of derivatization reagents and detection sensitivity of electrospray ionization-triple quadrupole tandem mass spectrometry: Hydrazines as prototypes

Highlights: • QSAR models were used to select derivatization reagents for ESI-MS analysis. • How modifying groups in the reagents affect the detection sensitivity of their derivatives was investigated by QSAR models. • Hydrophobicity, electronegativity, and molecular shape was important for rational design of derivatization reagents. • Detection sensitivity of a compound in SIM mode showed a positive correlation with that in MRM mode. Chemical derivatization-assisted electrospray ionization-triple quadrupole mass spectrometry (ESI-QqQ-MS) has become an efficient tool for the quantification of low-molecular-weight molecules. Many studies found that the derivatives of the same analytes derivatized by different derivatization reagents with the same reaction group had different detection sensitivity, even under the same conditions of electrospray ionization-mass spectrometry (ESI-MS). This phenomenon was suggested to be caused by the different modifying groups in the derivatization reagents. However, there is still a lack of systematic study on how modifying groups in the derivatization reagents affect the detection sensitivity of their corresponding derivatives of analytes, especially theoretical investigations. In this study, we employed a quantitative structure-activity relationship (QSAR) modeling approach to explore the relationship between modifying group structures and the detection sensitivity of derivatization reagents and their derivatives during ESI-MS detection. A total of 110 derivatization reagents of the hydrazine family and their hexanal derivatives (substituted hydrazones) were selected as the prototypes to construct QSAR models. The established models suggested that several molecular descriptors, related to hydrophobicity, electronegativity, and molecular shape, were related to the detection sensitivity of hexanal derivatives induced by different modifying groups in the derivatization reagents. Besides, we found that the detection sensitivity of compounds detected in selected ion mode (SIM) showed a positive correlation with that obtained in multiple reaction monitoring mode (MRM), and the ionization efficiency was the key factor on the detection sensitivity in both modes.