目的 运用液相色谱串联质谱（LC-MS/MS）技术建立尿液中硫酸软骨素(CS)、硫酸皮肤素(DS)和硫酸乙酰肝素(HS)含量的检测方法，探究该方法在黏多糖贮积症（MPS）患者诊断及治疗随访中的应用。方法 收集20例MPS患儿及37例正常儿童尿液样本，测定尿液中CS、DS和HS等浓度。尿样氮气吹干，盐酸甲醇衍生化，再次氮气吹干，复溶后LC-MS/MS分析；评价方法的线性、定量限、精密度、加样回收率和基质效应。结果 LC-MS/MS检测CS、DS和HS的线性均大于0.99。CS、DS和HS的定量下限依次为：0.5、1.0和1.0 mg/L。批内不精密度为1.9％~10.4％，批间不精密度为2.6％~9.8％。加标回收率为85.6％~110.4％，相对基质效应为84.9%~115.5%。CS、DS和HS在正常儿童尿液中呈正态分布，以 x+1.64 SD计算正常儿童尿液中的参考区间上限，分别为16.5、1.8、1.4 mg/mmol。通过分析MPS患儿尿液黏多糖特点，LC-MS/MS法能有效检出MPS I、MPS Ⅱ、MPS Ⅲ和MPS Ⅵ等MPS患儿。已接受造血干细胞移植的MPS Ⅰ和MPS Ⅱ患儿尿DS、HS水平降低。结论 LC-MS/MS检测尿黏多糖性能良好，有望用于MPS患者的精准诊断和治疗随访监测。

Objective To establish a method to determine chondroitin sulfate (CS), dermatan sulfate (DS) and heparan sulfate (HS) in urine by liquid chromatography tandem mass spectrometry (LC-MS/MS), and to investigate the application of urine glycosaminoglycans detection in the diagnosis and follow-up of mucopolysaccharidosis (MPS) patients. Methods Twenty urine samples from MPS patients and 37 urine samples from normal children were collected, and glycosaminoglycans levels in these samples were determined. Urine samples were added and dried under nitrogen. Then the samples were derivatized with methanol hydrochloride and dried under nitrogen. After reconstituted, the glycosaminoglycans were analyzed by LC-MS/MS. The linearity, limit of quantification, precision, spiked recoveries, and matrix effect were evaluated. Results The linearity of CS, DS and HS by LC-MS/MS was>0.99. The limits of quantification for CS, DS and HS were 0.5 mg/L, 1 mg/L and 1 mg/L, respectively; the intra-day imprecision ranged from 1.9% to 10.4%, and the inter-day imprecision ranged from 2.6% to 9.8%; and the recovery ranged from 85.6% to 110.4%, the relative matrix effect ranged from 84.9% to 115.5%. CS, DS and HS in urine samples of normal children were normally distributed, then the upper limit of reference interval were preliminarily determined by mean+1.64 SD, which were 16.5 mg/mmol, 1.8 mg/mmol and 1.4 mg/mmol, respectively. Urine GAGs of MPS patients were analyzed, the LC-MS/MS method was effective in detecting MPSⅠ, MPSⅡ, MPSⅢ and MPSⅥ patients. Urine samples of MPSⅠ or MPSⅡ patients who had hematopoietic stem cell transplantation showed reduced DS and HS concentration. Conclusion LC-MS/MS has good performance in detecting urinary mucopolysaccharides and is expected to be used for accurate diagnosis and treatment follow-up monitoring of MPS patients.