Analytical Sciences

Development of Highly Sensitive Analysis Method for Histamine and Metabolites in Pregnant Women’s Fingernail by UPLC-ESI-MS

Qingkun MA,* Aoi UCHIBE,** Qing SHI,* Toshimasa TOYO’OKA,** Chun-Yan XU,* and Jun Zhe MIN*

*Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy Yanbian University and Department of Pharmacy, Yanbian University Hospital, Yanji 133002, Jilin Province, China
**Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga, Shizuoka 422-8526, Japan

In this study, a highly sensitive analysis method for the rapid detection of histamine (HA), imidazole-4-acetic acid (IAA) and 1-methylhistamine (MHA) in pregnant women’s fingernails was developed using the ultra-performance liquid chromatography (UPLC) coupled with electrospray ionization tandem mass spectrometry (ESI-MS/MS). HA and MHA were connected with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) as the derivation reagent for the first time. IAA was derivatized with 4-(N,N-dimethylaminosulfonyl)-7-piperazino-2,1,3-benzoxadiazole (DBD-PZ) successfully. The derivative mixtures were simultaneously separated within 8 min on an ACQUITY UPLC^TM BEH C18 column (1.7 μm, 100 × 2.1 mm i.d.) by isocratic elution using a mixture of 20 mM HCOONH₄ and CH₃CN (82:18) as the mobile phase, and sensitively detected by selected reaction monitoring (SRM). The quantitative analysis of HA, IAA, and MHA are performed by SRM using the fragmentation transitions of m/z 337.2 → 292.1, 420.6 → 375.1 and 351.2 → 306.0 under the positive ESI mode. The calibration curves for HA, IAA and MHA are presented herein, and their correlation coefficient were found to be above 0.9998, the measured detection limit for derivatized histamine and metabolites ranged from 0.06 to 0.15 fmol, and the relative standard derivation of intra-day and inter-day assays was 6.3%. Furthermore, the mean recoveries (%) of the standards added to human fingernails were in the range of 90.2 – 100.5%. The validated method was successfully applied to analyze human fingernail samples from three pregnant women and three healthy non-pregnant women. To the best of our knowledge, this report about the detection of histamine and metabolites in the fingernails of pregnant women’s fingernails is the first published.

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