ESI-MS/MS를 이용한 소변 중 Globotriaosylceramide(Gb3)의 정량 및 임상 응용; 패브리병(Fabry) 진단

• 영문명: Method Development for the Profiling Analysis of Urine Globotriaosylceramide (Gb3) for the Screening of Fabry Disease by Tandem Mass Spectrometry
• 발행기관: 대한약학회
• 저자명: 윤혜란(Hye Ran Yoon) 조경희(Kyung Hee Cho) 강승우(Seung Woo Kang) 권영주(Young Joo Kwon) 정춘식(Chon Sik Jeong) 이용수(Yong Soo Lee)
• 간행물 정보: 『약학회지』제51권 제2호 (2007년), 96~102쪽, 전체 7쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2007.04.30

영문 초록

Measurement of globotriaosylceramide (Gb3, ceramide trihexoside) in urine has clinical importance for monitoring after enzyme replacement therapy in Fabry disease patients. The disease is an X-linked lipid storage disorder that results from a deficiency of the enzyme α-galactosidase A (α-Gal A). The lack of α-Gal A causes an intracellular accumulation of glycosphingolipids, mainly Gb3. A simple, rapid, and highly sensitive analytical method for Gb3 in urine was developed without labor-extensive pre-treatment by electrospray ionization MS/MS (ESI-MS/MS). Only simple 5-fold dilution of urine is necessary for the extraction and isolation of Gb3 in urine. Gb3 in diluted urine was dissolved in dioxane containing C17:0 Gb3 as an internal standard. After centrifugation it was directly injected and analyzed through guard column by in combination with multiple reaction monitoring mode of ESI-MS/MS. Eight isoforms of Gb3 were completely resolved from urine matrix. C24:0 Gb3 occupied 50% of total Gb3 as a major component in urine. Linear relationship for Gb3 isoforms was found in the rage of 0.005~5.0㎍/㎖. The limit of detection (S/N=5) was 0.005㎍/㎖ and limit of quantification was 0.05㎍/㎖ for C24:0 Gb3 with acceptable precision and accuracy. Correlation coefficient of calibration curves for 8 Gb3 isoforms ranged from 0.9598 to 0.9975. This method could be useful for rapid and sensitive 1st line Fabry disease screening, monitoring and/or diagnostic tool for Fabry disease.

키워드

quantification globotriaosylceramide(Gb3) MS/MS fabry disease screening