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Development of a Highly Sensitive and Rapid Liquid Chromatography- Tandem Mass Spectrometric Method Using a Basic Mobile Phase Additive to Determine the Characteristics of the Urinary Metabolites for Niemann-Pick Disease Type C
Maekawa, Masamitsu; Miyoshi, Keitaro; Narita, Aya; Sato, Toshihiro; Sato, Yu; Kumondai, Masaki; Kikuchi, Masafumi; Higaki, Katsumi; Okuyama, Torayuki; Eto, Yoshikatsu; Sakamaki, Hiroshi; Mano, Nariyasu
通讯作者Maekawa, M
来源期刊BIOLOGICAL & PHARMACEUTICAL BULLETIN
ISSN0918-6158
EISSN1347-5215
出版年2022
卷号45期号:9页码:1259-1268
英文摘要As Niemann-Pick disease type C (NPC) is difficult to diagnose owing to its various clinical symptoms; biomarker tests have been developed. Previously, we revealed urinary sulfated cholesterol metabolites as noninvasive biomarkers for NPC. However, LC/tandem mass spectrometry (LC/MS/MS) requires long separation time and large urine volumes. Recently, a basic mobile phase was reported to increase the MS intensity. Thus, we developed a highly sensitive and rapid LC/MS/MS method for analyzing urinary cholesterol metabolites using a basic mobile phase additive. 3 beta-Sulfooxy-7 beta-N-acetylglucosaminyl-5-cholenic acid, its glycine and taurine conjugates, 3 beta-sulfooxy-7 beta-hydroxy-5-cholenic acid, and 7-oxo form were measured, with selected reaction monitoring in negative ion mode. Oasis HLB and L-column 3 were used for column -switching LC/MS/MS and urine diluted 10-fold was employed as the sample. After trapping, gradient separation was performed using solutions containing 1% (v/v) ammonium solution. On average, a 16-fold increase in peak areas was observed compared to that obtained at pH 5.5 with the mobile phases. Although the previous method needed 60 min for separation from interference peaks, we succeeded to separate them in 7 min with optimized LC condition. Further, all compounds showed good linearity from 0.3-1000 ng/mL, with satisfactory intra-and inter-day reproducibility. The developed method was applied to the urinalysis of healthy participants and NPC patients. Overall, the concentrations of metabolites correlated with those obtained using the previous method. Therefore, we succeeded to increasing MS intensity and shorten LC running time; and the method is useful for the noninvasive diagnostic screening of patients with NPC.
英文关键词ammonium solution basic condition LC cholesterol metabolite urinary biomarker Niemann- Pick disease type C LC-electrospray ionization-tandem mass spectrometry
类型Article
语种英语
开放获取类型gold
收录类别SCI-E
WOS记录号WOS:000864075300007
WOS关键词LC/ESI-MS/MS ANALYSIS ; BILE-ACID ; LC-MS/MS ; MAJOR SPHINGOLIPIDS ; INBORN-ERRORS ; HUMAN PLASMA ; BIOMARKERS ; IDENTIFICATION ; DIAGNOSIS ; ESTERIFICATION
WOS类目Pharmacology & Pharmacy
WOS研究方向Pharmacology & Pharmacy
资源类型期刊论文
条目标识符http://119.78.100.177/qdio/handle/2XILL650/391975
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GB/T 7714
Maekawa, Masamitsu,Miyoshi, Keitaro,Narita, Aya,et al. Development of a Highly Sensitive and Rapid Liquid Chromatography- Tandem Mass Spectrometric Method Using a Basic Mobile Phase Additive to Determine the Characteristics of the Urinary Metabolites for Niemann-Pick Disease Type C[J],2022,45(9):1259-1268.
APA Maekawa, Masamitsu.,Miyoshi, Keitaro.,Narita, Aya.,Sato, Toshihiro.,Sato, Yu.,...&Mano, Nariyasu.(2022).Development of a Highly Sensitive and Rapid Liquid Chromatography- Tandem Mass Spectrometric Method Using a Basic Mobile Phase Additive to Determine the Characteristics of the Urinary Metabolites for Niemann-Pick Disease Type C.BIOLOGICAL & PHARMACEUTICAL BULLETIN,45(9),1259-1268.
MLA Maekawa, Masamitsu,et al."Development of a Highly Sensitive and Rapid Liquid Chromatography- Tandem Mass Spectrometric Method Using a Basic Mobile Phase Additive to Determine the Characteristics of the Urinary Metabolites for Niemann-Pick Disease Type C".BIOLOGICAL & PHARMACEUTICAL BULLETIN 45.9(2022):1259-1268.
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