A review of analytical parameters in ‘rapid’ liquid chromatographic methods for bioanalysis: Can we do better?

• Published in: Journal of Chromatography A Vol. 1721; p. 464803
• Main Authors: Lawlor, K, Clausen, J, Johnston, A, Edge, A, Wolff, K, Castrignanò, E, Couchman, L
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 26.04.2024
• Subjects: Bioanalysis; Chromatography, High Pressure Liquid - methods; Chromatography, Liquid - methods; Liquid chromatography; Mass spectrometry; Mass Spectrometry - methods; Plasma; Rapid; Urine; Urine; Plasma; Liquid chromatography; Bioanalysis; Rapid; Mass spectrometry
• ISSN: 0021-9673; 1873-3778
• DOI: 10.1016/j.chroma.2024.464803

•For many applications there are benefits to be gained in reducing analysis times.•The use of short LC columns (<50 mm) and high flow rates (exceeding 1 ml/min) is rare.•There appears to be a compromise between mass spectrometric ionisation efficiency at high flow rates and optimal chromatographic performance.•Matrice type, sample preparation, internal standard use (and chemistry) had little effect on analysis time.•MS data acquisition experiments, especially for high-resolution detectors, need to be considered carefully with rapid chromatographic separations. Rapid bioanalysis is beneficial to many applications. However, how ‘rapid’ a method is, or could be, is often an unanswered question. In this statistical review, the authors have assessed multiple pre-analytical (i.e. sample preparation), and analytical method parameters specifically for liquid chromatography to assist researchers in developing and validating ‘rapid’ bioanalytical methods. We restricted the search to urine and plasma matrices only. Data were extracted from over 2,000 recent studies and evaluated to assess how these parameters affected the ‘on-instrument’ analysis time. In addition to methods using ultra-violet (UV) detection, there were a large number of mass spectrometric (MS) methods, allowing additional review of the differences between high- and low-resolution MS on analysis time. We observed that most (N = 922, 70 %) methods used 5 or 10 cm columns, and that whilst uptake of ultra-high performance (U)HPLC columns was good, the use of sub-5 cm columns and/or flow rates in excess of 1 mL/min was incredibly rare (N = 25, 3 %). The detector of choice for quantitative (U)HPLC-MS remains the triple quadrupole, although a number of groups report the use of high-resolution MS for such methods.