Parker Suzanne L, Lipman Jeffrey, Dimopoulos George, Roberts Jason A, Wallis Steven C
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia; Department of Intensive Care Medicine, Royal Brisbane Hospital, Brisbane, Australia; Faculty of Health, Queensland University of Technology, Brisbane, Australia.
J Pharm Biomed Anal. 2015 Nov 10;115:509-14. doi: 10.1016/j.jpba.2015.07.013. Epub 2015 Jul 19.
Quantification of fosfomycin in the plasma samples of patients is the basis of clinical pharmacokinetic studies from which evidence based dosing regimens can be devised to maximise antibiotic effectiveness against a pathogen. We have developed and validated a LC-MS/MS method to quantify fosfomycin using dried plasma spot sampling. Following HILIC chromatography, fosfomycin and ethylphosphonic acid, used as internal standard, were measured using negative-ion multiple reaction monitoring. The method was linear over the calibration range of 5-2000mg/L of fosfomycin. Intra-day assay results for dried plasma spot quality control samples at 15.6, 79.9 and 1581mg/L of fosfomycin had precision of ±4.2, 8.2, and 2.0%, respectively, and accuracy of +3.9, -0.1, and -1.2%, respectively. Recovery of fosfomycin from dried plasma spots was calculated as 83.6% and the dried plasma spot samples were found to be stable stored at room temperature for three months and when stored for four hours at 50°C. A Bland-Altman plot comparing DPS to plasma sampling found a negative bias of 16.6%, with all but one sample within the mean limits of agreement (-2.6 to 30.6%). Dried plasma spot sampling provides a useful tool for pharmacokinetic research of fosfomycin.
对患者血浆样本中的磷霉素进行定量分析是临床药代动力学研究的基础，据此可制定循证给药方案，以最大限度地提高抗生素对病原体的有效性。我们开发并验证了一种使用干血浆斑样采样来定量磷霉素的液相色谱-串联质谱法。在亲水相互作用色谱之后，使用负离子多反应监测法测量磷霉素和用作内标物的乙基膦酸。该方法在磷霉素5-2000mg/L的校准范围内呈线性。干血浆斑样质量控制样品在磷霉素浓度为15.6、79.9和1581mg/L时的日内分析结果，精密度分别为±4.2%、8.2%和2.0%，准确度分别为+3.9%、-0.1%和-1.2%。从干血浆斑样中回收的磷霉素计算为83.6%，发现干血浆斑样在室温下储存三个月以及在50°C下储存四小时均稳定。比较干血浆斑样与血浆采样的Bland-Altman图显示负偏差为16.6%，除一个样品外，所有样品均在一致性平均限度内（-2.6至30.6%）。干血浆斑样采样为磷霉素的药代动力学研究提供了一种有用的工具。
