Validation of atovaquone plasma levels by liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring in pediatric patients.

Background: Atovaquone has traditionally been used as an antiparasitic and antifungal agent, but recent studies have shown its potential as an anticancer agent. The high variability in atovaquone bioavailability highlights the need for therapeutic drug monitoring, especially in pediatric patients. The goal of our study was to develop and validate the performance of an assay to quantify atovaquone plasma concentrations collected from pediatric cancer patients using LC-MS/MS. Methods: Atovaquone was extracted from a 10 µL volume of K2-EDTA human plasma using a solution consisting of ACN: EtOH: DMF (8:1:1 v:v:v), separated using reverse-phase chromatography, and detected using a SCIEX 5500 QTrap MS system. LC-MS/MS assay performance was evaluated for precision, accuracy, carryover, sensitivity, specificity, linearity, and interferences. Results: Atovaquone and its deuterated internal standard were analyzed using a gradient chromatographic method that had an overall cycle-time of 7.4 min per injection, and retention times of 4.3 min. Atovaquone was measured over a dynamic concentration range of 0.63 - 80 µM with a deviation within ≤ ± 5.1 % of the target value. Intra- and inter-assay precision were ≤ 2.7 % and ≤ 8.4 %, respectively. Dilutional, carryover, and interference studies were also within acceptable limits. Conclusions: Our studies have shown that our LC-MS/MS-based method is both reliable and robust for the quantification of plasma atovaquone concentrations and can be used to determine the effective dose of atovaquone for pediatric patients treated for AML.

Processable dispersions of photocatalytically active nanosheets derived from titanium diboride: self assembly into hydrogels and paper-like macrostructures.

Titanium diboride (TiB2), a layered ceramic material, is well-known for its ultrahigh strength, wear resistance, and chemical inertness. In this work, we present a simple one-pot chemical approach that yields sheet-like nanostructures from TiB2. We serendipitously found that TiB2 crystals can undergo complete dissolution in a mild aqueous solution of H2O2 under ambient conditions. This unexpected dissolution of TiB2 is followed by non-classical recrystallization that results in nanostructures with sheet-like morphology exhibiting Ti-O and B-O functional groups. We show that this pathway can be used to obtain an aqueous dispersion of nanosheets with concentrations ≥3 mg mL-1. Interestingly, these nanosheets tend to transform into a hydrogel without the need of any additives. We found that the degree of gelation depends on the ratio of TiB2 to H2O2, which can be tuned to achieve gels with a shear modulus of 0.35 kPa. We also show this aqueous dispersion of nanosheets is processable and forms hierarchical paper-like macrostructures upon vacuum filtration. Such an ability to assemble into free-standing 3D structures would enable a leap to practical applications. We also show that the high surface area and presence of oxy-functional groups on these nanosheets endow them a superior photocatalytic activity to degrade organic pollutants. This exemplifies the rich potential that TiB2 offers upon nanoscaling. The results presented here not only add a novel material to the 2D flatland but also urge the scientific community to revisit the chemistry of metal borides, that have been traditionally considered as relatively inert ceramics.

Boron based nanosheets as reducing templates in aqueous solutions: towards novel nanohybrids with gold nanoparticles and graphene.

We show that nanosheets obtained by exfoliating magnesium diboride bear an intrinsic ability to elicit chemical reduction of quinone-based molecules. They also reduce gold salt into ultra-small gold nanoparticles and graphene oxide into reduced graphene oxide. These nanosheets subsequently interface with the partner nanomaterial in solution to form novel nanohybrids.

Adult onset folliculocentric langerhans cell histiocytosis confined to the scalp.

Langerhans cell histiocytosis (LCH) is a pleomorphic disease entity characterized by local or disseminated atypical Langerhans cells found most commonly in bone, lungs, mucocutaneous structures, and endocrine organs. Cutaneous disease occurs in approximately one quarter of all cases. Cutaneous findings include soft-tissue swelling, eczematous changes, a seborrheic dermatitis-like appearance, and ulceration. We report a rare case of LCH confined to the scalp with folliculocentric infiltrates. This 32-year-old male patient presented with follicularly based erythema, scale, and pustules unresponsive to topicals and oral antibiotics. The patient's lesions mimicked lichen planopilaris and folliculitis decalvans during the disease process. On hematoxylin and eosin stain, scalp biopsy showed a perivascular interstitial patchy lichenoid mononuclear cell infiltrate that focally abutted follicular infundibula. Prominent mononuclear cells having reniform nuclei were present, and immunoperoxidase stains for CD1a confirmed Langerhans cell differentiation. Serological and imaging workup failed to display systemic involvement.