An ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was successfully developed and qualified for the simultaneous determination of triamcinolone hexacetonide (TAH) and triamcinolone acetonide (TAA, the active metabolite of TAH) in rabbit plasma. To prevent the hydrolysis of TAH to TAA ex vivo during sample collection and processing, we evaluated the effectiveness of several esterase inhibitors to stabilize TAH in plasma. Phenylmethanesulfonyl fluoride (PMSF) at 2.0 mM was chosen to stabilize TAH in rabbit plasma. The developed method is highly sensitive with a lower limit of quantitation of 10.0 pg/mL for both TAA and TAH using a 300 μL plasma aliquot. The method demonstrated good linearity, accuracy, precision, sensitivity, selectivity, recovery, matrix effects, dilution integrity, carryover, and stability. Linearity was obtained over the range of 10-2500 pg/mL. Both intra- and inter-run coefficients of variation were less than 9.1% and accuracies across the assay range were all within 100 ± 8.4%. The run time is under 5 minutes. The method was successfully implemented to support a rabbit pharmacokinetic study of TAH and TAA following a single intra-articular administration of TAH (Aristospan®).

A recent trial demonstrated that patients with knee osteoarthritis treated with a sodium hyaluronate and corticosteroid combination (Cingal) experienced greater pain reductions compared with those treated with sodium hyaluronate alone (Monovisc) or saline up to 3 weeks postinjection. In this study, injections were administered by 1 of 3 approaches; however, there is currently no consensus on which, if any, of these techniques produce a more favorable outcome. To provide additional insight on this topic, the results of the previous trial were reanalyzed to determine whether (1) the effect of Cingal was significant within each injection technique and (2) pain reductions were similar between injection techniques across all treatment groups. Greater pain reductions with Cingal up to 3 weeks were only significant in the anteromedial subgroup. Across all therapies, both the anteromedial and anterolateral techniques demonstrated significantly greater pain reductions than the lateral midpatellar approach at 18 and 26 weeks.