Development of a certified reference material for the accurate analysis of the acrylamide content in infant formula.

A certified reference material (CRM), KRISS CRM 108-02-006, was developed for the accurate analysis of low levels of acrylamide in infant formula matrices. The CRM is an infant formula fortified with acrylamide at a similar level as that stipulated by the European Union regulation for baby food. Commercially available infant formulas were processed by freeze-drying, and the subsequent homogenization of the fortified material to produce 961 bottles of the CRM in one batch. The CRM bottles containing approximately 15 g of the material in each unit were stored in a storage room at - 70 ℃. High-purity acrylamide was used as the primary reference material, and its purity was assessed using an in-house mass-balance method to obtain results metrologically traceable to the International System of Units. The acrylamide content of the infant formula CRM was evaluated using isotope dilution-liquid chromatography/mass spectrometry as a reference method, which was established by our research group. An acrylamide content of 55.7 ± 2.1 µg/kg was assigned as the certified value of the CRM with the expanded uncertainty at a 95% confidence level. The homogeneity study showed good uniformity of the acrylamide content among units, providing a relative standard deviation of 1.2% of the mean value. A stability study was also performed by monitoring the CRM under different temperature conditions and periods. The stability results indicated that the acrylamide content in the CRM under the storage conditions of - 70 ℃ remained stable for up to 10 months.

Perfluorooctanesulfonate Can Cause Negative Bias in Creatinine Measurement in Hemodialysis Patients Using Polysulfone Dialysis Membranes.

Serum creatinine is an important clinical marker for renal clearance. However, two conventional methods (Jaffe and enzymatic) are prone to interferences with organic compounds as compared to the standard method (isotope dilution-liquid chromatography-mass spectrometry) and can cause a significant negative bias. Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) are two common perfluorochemicals (PFCs) that can easily be accumulated in humans. We aimed to verify whether this bias is the result of an accumulation of PFCs. The serum creatinine values of 124 hemodialysis patients were analyzed using the three methods. We also aimed to evaluate which biochemical parameters will influence the difference between the conventional methods and the standard method. We found that a significant underestimation occurred when using the conventional methods. Albumin is an independent factor associated with negative bias, but it loses this correlation after dialysis, likely due to the removal of protein-bound uremic toxins. PFOS can cause negative bias when using the enzymatic method. Furthermore, this linear correlation is more significant in patients who used polysulfone-based dialysis membranes, possibly due to the better clearance of other uremic toxins. The serum creatinine of uremic patients can be significantly underestimated when using conventional methods. PFCs, as well the type of dialysis membrane being used, can be influencing factors.

Creatinine standardization: a key consideration in evaluating whole blood creatinine monitoring systems for CKD screening.

Early detection of CKD using point of care creatinine and eGFR testing improves patient management outcomes. We undertook a field study to evaluate the use of a whole blood creatinine/eGFR device to screen a rural Nicaraguan population to determine the variability between creatinine methods and specimen types. All specimens including capillary and venous dried blood spots (DBS) were tested with an isotope dilution liquid chromatography mass spectrometry (ID-LCMS) gold standard method. This is to our knowledge the first time a capillary whole blood (POC) method has been directly compared to the gold standard IDMS method, through the novel approach of using dried blood spots. Capillary and venous whole blood specimens were obtained and tested directly with the BCMS method, and then, DBS samples were prepared. Venous plasma specimens were tested using three laboratory analyzer creatinine methods. DBS were sent to the site performing ID-LCMS. Control samples were also prepared to assess the stability of shipment and storage of DBS. The ID-LCMS method was aligned using primary and secondary standards. Sixty-six (66) patients participated in the study, and the CKD prevalence rate was 7.8%. While all creatinine methods showed a good correlation to ID-LCMS, there was a positive bias (mean absolute bias range: 0.21-0.63 mg/dL). All methods used were 100% sensitive, but specificity varied from 62.7 to 94.9% with PPV ranging from 25 to 62.5%. A correction factor was used to align the values from each method to ID-LCMS which improved the specificity of each method. This study used a unique DBS approach to align capillary whole blood creatinine to ID-LCMS. To ensure reliability of BCMS for identifying screened patients with CKD, it is important to establish IDMS traceability and alignment prior to undertaking CKD studies.

Assessment of the performance of blood glucose monitoring systems for monitoring dysglycaemia in neonatal patients.

OBJECTIVE: To validate a three-step protocol that assesses the clinical risk associated with using blood glucose monitoring systems (BGMS) in neonates for the management of dysglycaemia. METHOD: The three-step validation approach included confirmation of the accuracy of the reference method using National Institute of Standards and Technology (NIST) glucose standards, assessment of analytical risk performed on whole blood collected from paediatric patients routinely tested for glucose and a clinical risk assessment performed using heel stick capillary samples collected from 147 new-born babies and neonates admitted to intensive care. BGMS glucose measurements were compared with the NIST aligned laboratory reference method. RESULTS: The accuracy of the laboratory reference method was confirmed with the NIST standards. Specificity studies demonstrated that the accuracy of one of the BGMS was affected, particularly, in the hypoglycaemic range, by known interference factors including haematocrit, ascorbic acid, lactose, galactose, N-acetylcysteine and glutathione. The accuracy of the other BGMS was unaffected. The clinical performance of this BGMS in neonates met the system accuracy criteria of Clinical and Laboratory Standards Institute (CLSI) POCT 12-A3 standard for evaluating hospital BGMS with 95.1% of glucose measurements within±0.67 mmol/L for samples ≤5.55 mmol/L and 95.6% within±12.5% for samples>5.55 mmol/L. CONCLUSIONS: This three-step validation protocol provides a challenging approach for determining the accuracy and reliability of BGMS for managing dysglycaemia in neonates. StatStrip BGMS achieved analytical and clinical performance criteria confirming its suitability for use in neonates. We advocate that this validation approach should be considered for performance evaluations of both BGMS and continuous glucose monitoring systems going forward.

Testicular vs adrenal sources of hydroxy-androgens in prostate cancer.

Neoadjuvant androgen deprivation therapy (NADT) is one strategy for the treatment of early-stage prostate cancer; however, the long-term outcomes of NADT with radical prostatectomy including biochemical failure-free survival are not promising. One proposed mechanism is incomplete androgen ablation. In this study, we aimed to evaluate the efficiency of serum hydroxy-androgen suppression in patients with localized high-risk prostate cancer under NADT (leuprolide acetate plus abiraterone acetate and prednisone) and interrogate the primary sources of circulating hydroxy-androgens using our recently described stable isotope dilution liquid chromatography mass spectrometric method. For the first time, three androgen diols including 5-androstene-3ß,17ß-diol (5-adiol), 5α-androstane-3α,17ß-diol (3α-adiol), 5α-androstane-3ß,17ß-diol (3ß-adiol), the glucuronide or sulfate conjugate of 5-adiol and 3α-adiol were measured and observed to be dramatically reduced after NADT. By comparing patients that took leuprolide acetate alone vs leuprolide acetate plus abiraterone acetate and prednisone, we were able to distinguish the primary sources of these androgens and their conjugates as being of either testicular or adrenal in origin. We find that testosterone, 5α-dihydrotestosterone (DHT), 3α-adiol and 3ß-adiol were predominately of testicular origin. By contrast, dehydroepiandrosterone (DHEA), epi-androsterone (epi-AST) and their conjugates, 5-adiol sulfate and glucuronide were predominately of adrenal origin. Our findings also show that NADT failed to completely suppress DHEA-sulfate levels and that two unappreciated sources of intratumoral androgens that were not suppressed by leuprolide acetate alone were 5-adiol-sulfate and epi-AST-sulfate of adrenal origin.