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Aim: Caffeine is a central nervous system stimulant, used to treat apnea of prematurity. A hydrophilic interaction chromatography–tandem mass spectrometry (HILIC-MS/MS) approach was developed to detect caffeine, paraxanthine, theophylline and theobromine in premature infants. Method: Protein precipitation of plasma samples (10 μl) was carried out by treating with acetonitrile containing caffeine-13C3. The separation was carried out on an ACQUITY HPLC® BEH HILIC column. Caffeine and its metabolites were quantified by multiple reaction monitoring modes with positive electrospray ionization. Results: The established method had a good linear relationship in the range of 0.0600–60.0 μg/ml for caffeine, 0.0250–7.50 μg/ml for theobromine and 0.0150–4.50 μg/ml for paraxanthine and theophylline. Conclusion: A HILIC-MS/MS method was developed and validated to determine caffeine and its major metabolites in plasma of premature infants.

Pivmecillinam, the ester of biologically active antibiotic mecillinam, is an effective oral preparation to treat urinary tract infections. To study pharmacokinetics in humans, LC-MS/MS methods were developed to quantify pivmecillinam and mecillinam in human plasma, respectively. Considering cephalexin as internal standard, analytes were separated on UltimateXB-C18 columns after protein precipitation by acetonitrile. The mobile phase was composed of water containing 0.1% formic acid and methanol. The multiple reactions monitoring transitions of m/z 440.2→167.1, 326.1→167.1, and 348.1→158.1 were selected to inspect pivmecillinam, mecillinam, and the internal standard in positive ion mode. No apparent matrix effect was perceived. Linearities were obtained over calibration ranges of 0.0500-12.0 and 10.0-15,000 ng/mL, respectively. The intraday precisions were below 5.5%, the interday precisions were below 6.1%, and accuracies were within -8.1 to 13.0%. Stability tests were conducted and an acidification step was explored to enhance the stability of pivmecillinam and mecillinam. Further stability was validated under various storage and processing conditions. Both methods were applied to a pharmacokinetic study of pivmecillinam and mecillinam after oral administration of 400 mg pivmecillinam hydrochloride tablets in healthy Chinese subjects.

Aim: HCP002, a phosphate-modified derivative of voriconazole, can improve solubility without using the nephrotoxic solubilizer, sulfobutylether-β-cyclodextrin. To study pharmacokinetics in humans, LC-MS/MS methods to quantify HCP002 in human plasma and urine were developed and validated. Method: After protein precipitation by acetonitrile containing voriconazole-d3, HCP002 was separated on a ZORBAX SB-Aq column, and LCMS/MS analysis was performed in multi-response monitoring mode. Results: The analytical run time was 3 min. Linearity was observed over the ranges of 0.100–40.0 and 0.400–200 μg/ml in plasma and urine, respectively. Precision and accuracy were within acceptable limits. Sample stability was confirmed. Conclusion: Rapid and reproducible methods quantified HCP002 in urine, and plasma samples were established.

To analyze the predictive value of acute phase proteins (APPs) on the prognosis of patients with acute myeloid leukemia (AML).293 AML patients who met the study requirements from January 2015 to April 2021 were collected, their clinical characteristics and pre-treatment APPs levels ［including albumin (ALB), fibrinogen (FIB), C-reactive protein (CRP), Ferritin (FER)］ were followed up and investigated. Pearson correlation coefficient was used to analyze the correlation between APPs. Logistic regression was used to analyze the risk factors for mortality in AML patients. ROC curve was used to analyze the predictive value of APP for mortality in AML patients, and Kaplan-Meier survival analysis was used to compare the effect of APPs on complete remission (CR) rate, overall survival (OS), disease-free survival (DFS), and progression-free survival rate (PFS) of AML patients.Pearson correlation analysis showed that there were negative correlations between ALB and CRP (r=-0.134, P=0002), as well as ALB and FER (r=-0.148, P=0.001). There were correlations between FER and CRP (r=0361, P＜0.001), as well as FER and FIB (r=0.293, P＜0.001). Logistic regression analysis showed that advanced age (50 years) (OR=1.87, 95% CI=1.25-2.15, P＜0.001), relapse after treatment (OR=2.11, 95% CI=111-3.18, P=0.003), FLT3-ITD mutation (OR=2.59, 95% CI=1.10-4.12, P＜0.001), CRP≥524 mg/L (OR=1.21, 95% CI=1.02-2.14, P=0.024), CFA (CFA=CRP*FIB/ ALB)≥3 (OR=2.41, 95% CI=1.65-6.47, P＜0.001), and FER≥1145.58 mg/ml (OR=1.67, 95% CI=1.15-3.75, P＜0.001) were the risk factors for the survival of AML patients. ROC curve analysis showed that FER (AUC=0.752, 95% CI=0.681-0823, P＜0.001, the best cut-off value=1220.56 mg/ml) and CFA (AUC=0.804, 95% CI=0.741-0.868, P＜0.001, the best cut-off value=3.00) had higher predictive value for the survival of AML patients. The remission rate, PFS, DFS, and OS in the low CFA group (CFA≤3) were significantly higher than those in the high CFA group (CFA＞3), and the overall mortality rate was lower than that in the high CFA group; the remission rate, PFS, DFS, and OS in the low FER group (FER≤1220.56 mg/ml) were significantly higher than those in the high FER group (FER＞1220.56 mg/ml), while the overall mortality rate was lower than that in the high FER group, and the difference is statistically significant.The CFA value and FER level before treatment in AML patients can independently predict the prognosis of patients, and high levels of CFA and FER are associated with poor prognosis of AML patients.急性期蛋白对急性髓系白血病患者预后的预测价值.分析急性期蛋白(APPs)对急性髓系白血病（AML）患者预后的预测价值.收集2015年1月-2021年4月符合研究要求的293例AML患者，随访并调查其临床特征和治疗前APP［包括白蛋白(ALB）、纤维蛋白原（FIB）、C-反应蛋白（CRP）、铁蛋白（FER）］。使用Pearson相关系数分析APP间的相关性，使用Logistic回归分析AML患者死亡的危险因素，使用ROC曲线分析APP对AML患者死亡的预测价值，使用Kaplan-Meier生存分析比较APP对AML患者的缓解（CR）率、总体生存期（OS）、无病生存期（DFS）、无进展生存期（PFS）的影响.相关性分析结果显示，ALB与CRP（r=-0.134，P=0.002）和FER（r=-0.148，P=0.001）间存在一定的负相关关系。FER与CRP（r=0.361，P＜0.001）和FIB（r=0.293，P＜0.001）间存在相关关系。Logistic回归分析显示，高龄（＞50岁）（OR=1.87，95% CI=1.25-2.15，P＜0.001）、治疗后复发（OR=2.11，95% CI=1.11-3.18，P=0003）、FLT3-ITD变异（OR=2.59，95% CI=1.10-4.12，P＜0.001）、CRP≥5.24 mg/L（OR=1.21，95% CI=1.02-2.14，P=0.024）、CFA（CFA=CRP*FIB/ALB）≥3（OR=2.41，95% CI=1.65-6.47，P＜0.001）、FER≥1145.58 mg/ml（OR=1.67，95% CI=1.15-3.75，P＜0.001）为AML患者生存的危险因素。ROC曲线分析显示，FER（AUC=0.752，95% CI=0.681-0.823，P＜0.001，最佳切点=1220.56 mg/ml）和CFA（AUC=0.804，95% CI=0.741-0.868，P＜0.001，最佳切点=3.00）对AML患者生存预测价值较高。低CFA组（CFA≤3）的CR率、PFS、DFS、OS均显著高于高CFA组（CFA＞3），而总体死亡率低于高CFA组；低FER组（FER≤1220.56 mg/ml）的CR率、PFS、DFS、OS均显著高于高FER组（FER＞1220.56 mg/ml），而总体死亡率低于高FER组，差异具有统计学意义.AML患者治疗前的CFA值和FER水平可独立预测患者的预后，高水平的CFA和FER与AML患者预后不良相关.