HPLC-UV Method Development and Validation to Monitor Difluprednate Synthesis.

During the synthesis of active pharmaceutical ingredients (APIs) there is a need for the development and validation of a simple and rapid high performance liquid chromatography (HPLC) method for the determination and quantification of the synthesized product and related by-products. An HPLC method gives a better understanding of how a synthesis is proceeding. A rapid and easy to use HPLC-UV (ultraviolet) method for the determination of difluprednate and monitoring of impurities generated during synthesis was developed and validated. A Shimadzu VP Series HPLC equipped with a LabSolutions software and UV detector set at 240 nm was used for analysis. The mobile phase consisted of phosphate buffer (pH 6) and acetonitrile 50:50 (v/v) and was eluted at a flow rate of 1.2 mL/min. Separation took place on a reversed-phase Kinetex C18 column (150 × 4.60 mm; 5 µm i.d.). Column temperature was set at 40°C. The developed method was found to have good linearity and acceptable accuracy and precision. The developed method may be effectively applied to determine products and by-products formed during synthetic reactions of steroids and to calculate the yield of the products obtained during each step of the synthesis.

The changing landscape of treatment options in childhood acute lymphoblastic leukaemia.

New paediatric acute lymphoblastic leukaemia (ALL) treatments have been developed and innovative products are in the pipeline. However, despite many active clinical trials, bridging bench science to clinical development to authorised medicines remains challenging. Research in first-line treatment continues to focus on multidrug chemotherapy with the potential addition of new targeted molecules being studied. Research in second- and third-line treatment represents a shift from cytotoxic intensification to an area of precision medicine through emergent innovative and immuno-oncology products. The collaborative research model in ALL involving different stakeholders should intensify to facilitate bench-to-bedside clinical translation for the benefit of patients.

Pharmaceuticals and the environment.

The marked progress and increase in the number of medications available for the treatment of conditions and diseases left a footprint on the surrounding environment. The consumption of medications for human and veterinarian use impact the terrestrial and marine environment and affects the ecosystem. The increase in environmental awareness regarding pharmaceutical related activities led to the development of principles and measures to mitigate a negative environmental impact. Various measures were introduced to promote green manufacturing and practices which led to the development of alternative techniques and processes, which are of benefit to both the environment and the industry. Distributors and pharmacists can contribute through the efficient management of everyday operations which include better stock taking and rotation, grouping deliveries and reducing unused medications. The incorporation of green practices in the pharmacy curriculum empowers future pharmacists with skills and competences required at the place of work to decrease the impact of processes and medicines on the environment. The presence of a pharmacist workforce which is more conscientious about the environment leads to the needed ripple effect to embrace and implement green principles in different pharmacy related settings. Patients should also be educated to avoid hoarding of medications and dispose of medication in a safe and appropriate manner. The implementation of green practices results in a decrease in the use of chemicals and production of waste which in turn leads to a decrease in pollutants which have an impact on climate change.

A three-year post-graduate Doctorate in Pharmacy course incorporating professional, experiential and research activities: A collaborative innovative approach.

This article was migrated. The article was marked as recommended. Background A three-year post-graduate international Doctorate in Pharmacy collaborative course, was launched by the Department of Pharmacy, University of Malta in collaboration with the College of Pharmacy, University of Illinois at Chicago. Aim and rationale To demonstrate that the professional Doctorate in Pharmacy (i) fits the requirements of a Level 8 degree according to the Bologna process, (ii) helps graduates develop competencies and attributes in proficiency in clinical and professional aspects, (iii) has a research component that provides the right level of abilities to participate in research initiatives and to interpret research outcomes, (iv) enables graduates to obtain leadership characteristics. Approach The unique characteristics of the course were evaluated through an outcomes result-oriented measurement. Leadership aspects were measured through policies and strategies presented by students and graduates. Outcomes i) course is in line with the Bologna declaration, ii) research work shown in the dissertation satisfied competencies required iii) research abilities have been examined through a third party and found to be compliant with acquiring of concepts in the design, carrying out, assessment of outcomes and interpretation of results of the research study carried out by each student, and iv) leadership characteristics were shown by the positions taken up by the graduates and early outcomes from these positions. Conclusion Learning activities enable development of professionals able to merge scientific and practice aspects in the evaluation of innovative therapies, the use of medicines and patient monitoring, and in pharmaceutical policy development and regulation. Leadership positions taken up by graduates point to the acquisition of leadership skills by graduates. Next Steps The authors are happy to extend collaboration for this model to be adapted by other institutions for the curricular development entailed in this programme to enhance and improve an innovative aspect in the evolvement of the pharmacy profession on the international scenario.

A multi-technique analytical approach for impurity profiling during synthesis: The case of difluprednate.

A methodology for the qualitative analysis of a mixture of compounds obtained during the synthesis of difluprednate is described herein for the first time. For this scope a multi-technique analytical approach was developed, combining Liquid Chromatography/Mass Spectrometry (LC/MS), Nuclear Magnetic Resonance (NMR) and computational chemistry. Separation of isomers is frequently required for the identification of impurities in active pharmaceutical ingredients (APIs) to assess the impact they may exhibit on public health. During the final step of the difluprednate synthesis apart from the desired product, various by-products may be obtained. Structural analysis of the products using LC/MS and NMR indicated that the steroid difluprednate was obtained along with its acetyl/butyryl regional isomers, whereas the results were further supported by semi-empirical calculations of the MS-derived data. Following the proposed approach, we managed to elucidate the structures of the challenging 11-acetate, 17-butyrate from the 17-acetate, 21-butyrate, 6α,9α-difluoro prednisolone isomers. The approach utilized may be of general applicability for the analysis of impurities in active pharmaceutical ingredients obtained during chemical synthesis.

Practical liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of amitriptyline, nortriptyline and their hydroxy metabolites in human serum.

Amitriptyline (AMI) has been in use for decades in treating depression and more recently for the management of neuropathic pain. A highly sensitive and specific LC-tandem mass spectrometry method was developed for simultaneous determination of AMI, its active metabolite nortriptyline (NOR) and their hydroxy-metabolites in human serum, using deuterated AMI and NOR as internal standards. The isobaric E-10-hydroxyamitriptyline (E-OH AMI), Z-10-hydroxyamitriptyline (Z-OH AMI), E-10-hydroxynortriptyline (E-OH NOR) and Z-10-hydroxynortriptyline (Z-OH NOR), together with their parent compounds, were separated on an ACE C18 column using a simple protein precipitation method, followed by dilution and analysis using positive electrospray ionisation with multiple reaction monitoring. The total run time was 6 min with elution of E-OH AMI, E-OH NOR, Z-OH AMI, Z-OH NOR, AMI (+ deuterated AMI) and NOR (+ deuterated NOR) at 1.21, 1.28, 1.66, 1.71, 2.50 and 2.59 min, respectively. The method was validated in human serum with a lower limit of quantitation of 0.5 ng/mL for all analytes. A linear response function was established for the range of concentrations 0.5-400 ng/mL (r2 > .999). The practical assay was applied on samples from patients on AMI, genotyped for CYP2C19 and CYP2D6, to understand the influence of metaboliser status and concomitant medication on therapeutic drug monitoring.