Comparison of the MAAT and AHA test for PEG-ASE activity confirmed a mean difference of 23% between MAAT and AHA test for PEG-ASE activities between 30 and 600 U/L. The discrepancy increased in samples with >600 U/L PEG-ASE activity, which will be especially relevant when evaluating high PEG-ASE activities in relation to toxicity, efficacy, and population pharmacokinetics.

Aim To investigate the pharmacokinetics (PK) of intravenous treosulfan in paediatric patients undergoing haematopoietic stem cell transplantation (HSCT) for a broad range of diseases and to explore the impact of different dosing regimens on treosulfan exposure (area under the concentration–time curve, AUC0→∞) through dosing simulations. Methods A prospective multicentre PK study was conducted using treosulfan concentration data (n = 423) collected from 53 children (median age 3.5, range 0.2–17.0 years) receiving three daily age‐guided doses (10–14 g/m2). Population PK modelling was performed using NONMEM software, utilising a stepwise forward selection backward elimination method and likelihood‐ratio test for screening covariates to describe PK variability. Monte Carlo simulation was used to generate patient PK data for 10 000 virtual paediatric patients and cumulative AUC0→∞ values were evaluated using age, body surface area (BSA) and model‐based dosing regimens, targeting 4800 mg*h/L. Results Treosulfan concentration data were described using a one‐compartment PK model with first‐order elimination. Population mean (95% CI) estimates for clearance (CL) and volume of distribution (V) were 16.3 (14.9–18.1) L/h and 41.9 (38.8–45.1) L, respectively. Allometrically scaled body weight was the best covariate descriptor for CL and V, and maturational age further explained variability in CL. Dosing simulations indicated that in young patient groups (<2 years), a model‐based dosing regimen more accurately achieved the target AUC0→∞ (58.3%) over the age (42.6%) and BSA‐based (51.3%) regimens. Conclusion Treosulfan disposition was described through allometric body weight and maturational age descriptors. Model‐informed dosing is recommended for patients under 2 years. Treosulfan PK parameters and AUC0→∞ were not influenced by patient disease.

Alectinib is a central nervous system-active small molecule anaplastic lymphoma kinase (ALK) inhibitor that is effective in the treatment of patients with ALK positive tumors, including advanced non-small cell lung cancers and lymphomas. A simple, isocratic high-performance liquid chromatography–photo diode array detection (HPLC–PDA) assay for measurement of alectinib in human plasma is described. Alectinib is extracted from the plasma matrix by addition of methanol, followed by centrifugation and acidification with 0.1% formic acid. It elutes with a run time of 4.6 min using a 250 mm × 4.6 mm RP-C18 column with 0.1% aqueous formic acid and methanol (35:65, v/v) and a flow rate of 1 mL/min. Detection was at 339 nm. Linear calibration plots were achieved in the range of 0.1–20 μg/mL for alectinib (r2 = 0.9996). With limits of detection and quantification of 0.05 and 0.1 μg/mL, respectively, and excellent precision (%CV < 10%), accuracy (bias < ±12%), and recovery (>97%) within the 1–20 μg/mL concentration range, this assay was suitable for measuring pre-dose alectinib concentrations in an adolescent receiving 600-mg doses twice daily.