Refrigerated Stability of Diluted Cisatracurium, Rocuronium, and Vecuronium for skin testing after perioperative anaphylaxis

Rationale: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing. Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions. Results: The results are measured as beyond use date (BUD) defined as recovery of drug versus the reference (90-110%). Based on the LC-MS/MS data, the BUD for cisatracurium diluted to 10x and 100x is 96 hours. Higher dilutions (1,000x to100,000x) should be used immediately following preparation (within less than 24 hours). Vecuronium at 10x and 100x, also has a BUD of 96 hours, and the 1,000x dilution is stable for 24 hours. The 10,000x dilution should be used immediately. Rocuronium at 10x to 1,000x has a BUD of 48 hours, yet higher dilutions (10,000x and 100,000x) should be used immediately. Conclusions: With increasing dilution factors, the stability of these drugs in saline decreases, increasing deviation between samples and references. The most stable dilutions for each of the drugs tested were 10x and 100x. Stability of these drugs is likely compromised by hydrolysis of the ester bonds in the drug molecules

Stability of Diluted Neuromuscular Blocking Agents Utilized in Perioperative Hypersensitivity Evaluation

Purpose: Neuromuscular blocking agents are a common cause of hypersensitivity reactions during surgery. An allergy evaluation, including skin testing of these drugs prior to future surgeries, may help prevent life threatening reactions. Drug concentrations utilized for skin testing vary by country and institution. The purpose of this study was to investigate the stored stability of clinically relevant dilutions of neuromuscular blocking agents (NMBAs), namely succinylcholine, atracurium, cisatracurium, rocuronium, pancuronium, and vecuronium, for skin prick/intradermal testing. Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x, as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed for analysis, and compared to a freshly prepared set of reference dilutions. Results: Acceptable potency of the stored preparations is defined as 90-110% of the initial drug concentration (versus a reference). All drugs were stable for at least 48 hours in the 1:10 dilution and for 24 hours in the 1:100 dilution. At higher dilution factors, the detectable amount of drug in the stored dilutions deteriorated rapidly, indicating that such preparations should be used immediately. Conclusion: With increasing dilution factors, the stability of these drugs in saline decreases, increasing deviation between samples and references. The most stable dilutions for each of the drugs tested were 10x and 100x

Refrigerated Stability of Diluted Cisatracurium, Rocuronium, and Vecuronium for Skin Testing after Perioperative Anaphylaxis

RATIONALE: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing. METHODS: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions. RESULTS: The results are measured as beyond use date (BUD) defined as recovery of drug versus the reference (90-110%). Based on the LC-MS/MS data, the BUD for cisatracurium diluted to 10x and 100x is 96 hours. Higher dilutions (1,000x to 100,000x) should be used immediately following preparation (within less than 24 hours). Vecuronium at 10x and 100x also has a BUD of 96 hours, and the 1,000x dilution is stable for 24 hours. The 10,000x dilution should be used immediately. Rocurium at 10x to 1,000x has a BUD of 48 hours, yet higher dilutions (10,000x and 100,000x) should be used immediately. CONCLUSIONS: With increasing dilution factors, the stability of these drugs in saline decreases, increasing deviation between samples and references. The most stable dilutions for each of the drugs tested were 10x and 100x. Stability of these drugs is likely compromised by hydrolysis of the ester bonds in the drug molecules

A SERRS-active bead/microelectromagnet system for small-scale sensitive molecular identification and quantitation

How do you catch and identify a molecule in a very dilute solution? The question is important for the detection of trace amounts of such molecules as explosives, drugs, and biomolecules. Here we use a specifically designed microelectromagnet and surface-enhanced resonance Raman microspectroscopy (see figure) to provide an answer to this question, advancing a technique that has advantages over other current technologies

Circulating tumor DNA as a clinical test in resected pancreatic cancer

Purpose: In research settings, circulating tumor DNA (ctDNA) shows promise as a tumor-specific biomarker for pancreatic ductal adenocarcinoma (PDAC). This study aims to perform analytical and clinical validation of a KRAS ctDNA assay in a Clinical Laboratory Improvement Amendments (CLIA) and College of American Pathology–certified clinical laboratory. Experimental Design: Digital-droplet PCR was used to detect the major PDAC-associated somatic KRAS mutations (G12D, G12V, G12R, and Q61H) in liquid biopsies. For clinical validation, 290 preoperative and longitudinal postoperative plasma samples were collected from 59 patients with PDAC. The utility of ctDNA status to predict PDAC recurrence during follow-up was assessed. Results: ctDNA was detected preoperatively in 29 (49%) patients and was an independent predictor of decreased recurrence-free survival (RFS) and overall survival (OS). Patients who had neoadjuvant chemotherapy were less likely to have preoperative ctDNA than were chemo-na€ve patients (21% vs. 69%; P < 0.001). ctDNA levels dropped significantly after tumor resection. Persistence of ctDNA in the immediate postoperative period was associated with a high rate of recurrence and poor median RFS (5 months). ctDNA detected during follow-up predicted clinical recurrence [sensitivity 90% (95% confidence interval (CI), 74%–98%), specificity 88% (95% CI, 62%–98%)] with a median lead time of 84 days (interquartile range, 25–146). Detection of ctDNA during postpancreatectomy follow-up was associated with a median OS of 17 months, while median OS was not yet reached at 30 months for patients without ctDNA (P ¼ 0.011). Conclusions: Measurement of KRAS ctDNA in a CLIA laboratory setting can be used to predict recurrence and survival in patients with PDAC