Comprehensive characterization and resolution of discrepant spectrophotometric bilirubin results in patients on eltrombopag therapy.

Background Eltrombopag is a thrombopoietin receptor agonist used for the treatment of thrombocytopenic conditions. It can cause pH-dependent discoloration of plasma/serum. Eltrombopag is potentially hepatotoxic. It can affect the assessment of hyperbilirubinemia because of its (i) absorbance at ~450 nm (bilirubin), (ii) absorbance at ~550 nm (diazo-bilirubin) and (iii) it can cause yellowish discoloration of the eyes at normal circulating bilirubin levels. Methods We collected 66 samples from patients on a range of eltrombopag dosages up to 150 mg daily. Bilirubin was measured using multiple routine spectrophotometric analyzers, the Doumas reference method and high-performance liquid chromatography (HPLC). Plasma/serum eltrombopag concentrations were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS). Spike-in and admixture experiments delineated the effects of eltrombopag and its metabolites. Results Forty-nine of 52 samples from patients on ≥50 mg daily eltrombopag therapy showed significantly discrepant inter-analyzer total bilirubin results, a difference up to 64 µmol/L (3.7 mg/dL). In one sample, total bilirubin varied from 8 to 65 µmol/L (0.4-3.8 mg/dL) by different routine analyzers, with direct bilirubin ≤4 µmol/L (0.2 mg/dL). There was a positive correlation between total bilirubin difference and plasma eltrombopag concentration (r = 0.679), and spike-in experiments demonstrated that Beckman AU and Doumas reference methods were susceptible to positive interference. HPLC can quantify bilirubin after separating eltrombopag, and results suggest different analyzers are affected to varying degrees by eltrombopag and its metabolites. Conclusions Eltrombopag and its metabolites can cause positive interference to the spectrophotometric measurements of total bilirubin. Accurate measurements of total bilirubin may improve our understanding of the prevalence of hyperbilirubinemia in patients on eltrombopag therapy.

Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia. Over the last decade, plasma Epstein-Barr virus (EBV) DNA has been developed as a tumor marker for NPC. In this study, the authors investigated whether plasma EBV DNA analysis is useful for NPC surveillance. METHODS: In total, 1318 volunteers ages 40 to 60 years were prospectively recruited. Plasma EBV DNA and serology for viral capsid antigen immunoglobulin A (IgA) were measured. Participants who had detectable plasma EBV DNA or positive IgA serology underwent nasal endoscopic examination and a follow-up plasma EBV DNA analysis in approximately 2 weeks. All participants were followed for 2 years to record the development of NPC. RESULTS: Three individuals with NPC were identified at enrolment. All of them were positive for EBV DNA and remained positive in follow-up analysis. Only 1 of those patients was positive for EBV serology. In 1 patient who had NPC with a small tumor confined to the mucosa, the tumor was not detectable on endoscopic examination. Because of a 2-fold increase in plasma EBV DNA on the follow-up analysis, that patient underwent magnetic resonance imaging, which revealed the tumor. Among the participants who did not have NPC but had initially positive plasma EBV DNA results, approximately 66% had negative EBV DNA results after a median of 2 weeks. CONCLUSIONS: Plasma EBV DNA analysis proved useful for detecting early NPC in individuals without a clinical suspicion of NPC. Repeating the test in those who had initially positive results differentiated those with NPC from those who had false-positive results. Cancer 2013. © 2013 American Cancer Society.

Pharmacogenetic analysis of lipid responses to rosuvastatin in Chinese patients.

Lipid changes with statin treatments vary greatly between individuals for reasons which are largely unknown. This study was performed to examine the genetic determinants of lipid responses to rosuvastatin in Chinese patients. A total of 125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed for association with the lipid responses to rosuvastatin 10 mg daily. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 gene (P=9.2×10), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 gene (P=0.0002), 1421C>G in the lipoprotein lipase gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II gene cluster (P=0.004). Patients with familial hypercholesterolemia had 2.6% smaller reductions in LDL-C compared with patients without familial hypercholesterolemia. This study identified some genetic determinants of LDL-C response to rosuvastatin in Chinese patients, which need to be replicated in other populations.

Performance of a point-of-care device for oral fluid ketamine evaluated by a liquid chromatography-tandem mass spectrometry method.

The performance of a point-of-care device, the OratectXP Oral Fluid Drug Screen Device for Ketamine, was evaluated. The cutoff specification for the device was for ketamine at 15 ng/mL. A total of 72 authentic oral fluid samples were collected from volunteers at two local rehabilitation centers for clients with addiction to drugs of abuse. These samples were tested with the device for visual detection of ketamine and also measured by a liquid chromatography isotope-dilution tandem mass spectrometry method for ketamine, norketamine and dehydronorketamine concentrations. Sensitivity of the device was 87.5% when tested by 24 authentic oral fluid samples with ketamine concentrations ≥ 15 ng/mL. False positive rate of the device was 4.5%. Specificity of the device was 97.9% when tested by 48 authentic oral fluid samples with ketamine concentrations < 15 ng/mL. False negative rate of the device was 6%. The overall efficiency of the device was 94%. According to the desirable acceptance criteria proposed by the "Driving Under the Influence of Drugs, Alcohol, and Medicines" project, the performance of the OratectXP was satisfactory and achieved the minimum standard for testing drivers under the influence of drugs. Furthermore, we propose the confirmation cutoff level for oral fluid ketamine to be at 25 ng/mL.

Cadmium and lead in Hong Kong school children.

AIM: Cadmium (Cd) and lead (Pb) are toxic elements in our environment. This study is to determine the reference intervals of Cd and Pb in blood and urine from Hong Kong school children and to identify their determinants. METHODS: A total of 2209 secondary school children and 893 preschool children were recruited. Cd and Pb in blood and urine were measured by inductively-coupled plasma mass spectrometry. RESULTS: Blood Cd was affected by age, smoking and residential district, while urine Cd was influenced by age and blood Cd. Blood Cd was positively correlated with smoking as confirmed by urinary cotinine (rho  = 0.183, p  <  0.001, n = 2074). Blood Pb was dependent on gender and residential district, while urinary Pb was dependent on gender and blood Pb. Students from schools of lower academic grading had higher blood Cd and Pb than those from higher academic grading schools (p < 0.001, respectively). Urinary albumin was positively associated with urinary Cd and Pb. CONCLUSIONS: Using a non-occupationally exposed population, the reference ranges are: blood Cd < 21.9  nmol/L for smokers and < 8.8  nmol/L for non-smokers, and blood Pb < 203.8  nmol/L. Reference intervals for urinary Cd and Pb are also reported.