Sample preparation is considered as the bottleneck step in bioanalysis because each biological matrix has its own unique challenges and complexity. Competent sample preparation to extract the desired analytes and remove redundant components is a crucial step in each bioanalytical approach. The matrix effect is a key hurdle in bioanalytical sample preparation, which has gained extensive consideration. Novel sample preparation techniques have advantages over classical techniques in terms of accuracy, automation, ease of sample preparation, storage, and shipment and have become increasingly popular over the past decade. Our objective is to provide a broad outline of current developments in various bioanalytical sample preparation techniques in chromatographic and spectroscopic examinations. In addition, how these techniques have gained considerable attention over the past decade in bioanalytical research is mentioned with preferred examples. Modern trends in bioanalytical sample preparation techniques, including sorbent-based microextraction techniques, are primarily emphasized.

Nucleic acid (NA)-based biopharmaceuticals have emerged as promising therapeutic modalities. NA therapeutics are a diverse class of RNA and DNA and include antisense oligonucleotides, siRNA, miRNA, mRNA, small activating RNA, and gene therapies. Meanwhile, NA therapeutics have posed significant stability and delivery challenges and are expensive. This article discusses the challenges and opportunities for achieving stable formulations of NAs with novel drug delivery systems (DDSs). Here we review the current progress in the stability issues and the significance of novel DDSs associated with NA-based biopharmaceuticals, as well as mRNA vaccines. We also highlight the European Medicines Agency (EMA) and US Food and Drug Administration (FDA)-approved NA-based therapeutics with their formulation profiles. NA therapeutics could impact future markets if the remaining challenges and requirements are addressed. Regardless of the limited information available for NA therapeutics, reviewing and collating the relevant facts and figures generates a precious resource for formulation experts familiar with the NA therapeutics’ stability profile, their delivery challenges, and regulatory acceptance.

Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability. However, some excipients are prone to degradation during repeated use and/or improper storage, and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored, affecting the stability of biopharmaceuticals. In this study, we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry (GC-MS). The other polyol excipient, mannitol, was much more stable than glycerol. The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide, thymopentin, were also evaluated. The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol, compared to 95.8% in other formulations after the stress test. Most glycerol impurities (i.e., aldehydes and ketones) reacted with thymopentin, affecting the stability of thymopentin formulations. In conclusion, this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage. Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

Prefilled dual chamber devices (DCDs) are combination products containing freeze-dried drug and diluent in two separate chambers of the device. DCDs provide high stability and convenience to patients and doctors, thus significantly improving product quality, patient compliance and market competitiveness. DCDs should also provide seal integrity, sterility and compatibility with biopharmaceuticals and avoid leachability and needle stick injuries. DCDs are promising alternatives to traditional containers or devices for biopharmaceuticals. The regulatory and medical practice to choose plastic DCDs as better alternatives over well-established glass syringes will be addressed here. The impact and major issues during processing, manufacturing, and storage of DCDs are also highlighted. Further discussion clears its business potential, composition, stability testing, and quality standard requirements to deal with market competition. It also covers major role of extractables and leachables in storage stability of the product.