Analysis of blood concentrations and clinical application of risdiplam in patients with spinal muscular atrophy using ultra-high performance liquid chromatography-tandem mass spectrometry.

Risdiplam, the first oral therapy approved for spinal muscular atrophy and made globally available in 2021, necessitates a highly sensitive and straightforward assay for therapeutic drug monitoring. This is crucial to manage potential toxicities linked to drug concentrations and supervise dosing regimens. A cutting-edge ultra-high performance liquid chromatography-tandem mass spectrometry bioassay for risdiplam in human serum has been developed. In this method, analytes were separated on a Phenomenex Kinetex XB C18 column using a 6.5-min gradient elution after a single-step protein precipitation. MS detection was conducted via electrospray ionization in positive mode with selected reaction monitoring. The validated range for risdiplam was determined to be 1.95-125.00 ng/mL. The precision and accuracy of intra- and inter-batch analyses were within ±15%. The novel method met all other established criteria. This assay holds promise for monitoring drug concentrations and guiding clinical decisions in patients with spinal muscular atrophy.

[The influence of GABAA receptor on the analgesic action of intrathecally injected oxysophoridine].

.This study is to investigate the analgesic effect produced by intrathecal injection (ith) of oxysophoridine (OSR) and the mechanism of GABAA receptor. Warm water tail-flick test was used to detect the analgesic effect of OSR (12.5, 6.25, and 3.13 mg.kg-1 ith) and to observe the influence of GABA (gamma aminobutyric acid) agonist or antagonist on the analgesic effect of OSR in mice. Immunohistochemistry method were used to detect the influence of OSR (12.5 mg.kg-1, ith) on the GABAARalpha1 protein expression in spinal cord. The results obtained covers that OSR (12.5 and 6.25 mg.kg-, ith) alleviates pain significantly with the warm water tail-flick test (P<0.05, P<0.01), the rate of pain threshold increases by 68.45%; GABA and muscimol (MUS) produces analgesic synergism together with the OSR, picrotoxin (PTX) and bicuculline (BIC) antagonize the analgesic effect of OSR; OSR (12.5 mg.kg-1, ith) significantly increase the positive number of GABAARalpha1 nerve cell in spinal cord (P<0.01) and significantly decrease the average grey levels (P<0.01). In conclusion, OSR intrathecal injection has significant analgesic effect. And GABAA receptor in spinal cord is involved in the analgesic mechanism.