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Biomedical subjects

J J Roy

Publications and source records attributed to J J Roy.

7 recordsLinked to original sources
PubMed2004

Physicochemical properties of neuromuscular blocking agents and their impact on the pharmacokinetic-pharmacodynamic relationship.

BACKGROUND: Among the factors influencing the onset of action of neuromuscular blocking agents (NMBA), the potency (EC50) and the rate of equilibration between blood and the effect compartment (k(e0)) have been highlighted. Although these descriptors are intrinsically influenced by the physicochemical characteristics of the drug, the impact of lipid solubility, molecular weight and protein binding on pharmacokinetic-pharmacodynamic (PK-PD) descriptors has not been established for most NMBA. METHODS: The octanol/phosphate buffer distribution coefficients (logD) of various NMBA (vecuronium, rocuronium, mivacurium isomers (cis-cis, cis-trans and trans-trans), doxacurium, cisatracurium, atracurium, succinylcholine) were determined. The free fraction for each drug was measured using an ultrafiltration technique. PK-PD descriptors were obtained from selected clinical studies. Correlations between physicochemical parameters (including molecular weight) and PK-PD descriptors were assessed by linear or multiple linear regression. RESULTS: A wide range of log D (-4.15 for succinylcholine to 0.75 for vecuronium) and free fraction (from 31% for vecuronium to 80% for succinylcholine) is observed for NMBA. Molecular weight combined with either lipid solubility (r2=0.70; P=0.001) or free fraction (r2=0.84; P<0.001) were highly correlated with potency, while for k(e0) a greater degree of correlation was obtained when both lipid solubility and free fraction (r2=0.74; P=0.002) were included. CONCLUSIONS: The basic characteristics of NMBAs, namely, molecular weight, lipid solubility and protein binding, are strongly associated with the kinetics of the drug response.

Chemical Phenomena↗
PubMed2001

Measurement of succinylcholine concentration in human plasma by electrospray tandem mass spectrometry.

An electrospray mass spectrometric method for the quantification of the depolarizing neuromuscular blocking agent succinylcholine (SUX) is described. An extraction method compatible with direct infusion inlet was developed and leads to an analysis cycle time of 7--8 min instead of 25 min that would be required for HPLC inlet. SUX was extracted from human plasma on C1 solid-phase cartridges and was analyzed using positive ion electrospray tandem mass spectrometry (ESI-MS/MS). SUX plasma concentrations were determined by a stable isotope dilution assay using hexadeuterosuccinylcholine diiodide (SUXd6) as the internal standard. The calibration curve was prepared using the ratio of intensities of the major product ions in the collision-induced dissociation spectrum for known concentration ratios of SUX and SUXd6 in plasma. Calibration curves for the quantification were linear from 25 to 4000 ng/ml. For intraday precision, CV were < or =6% and accuracy ranged from 98 to 103%. For the interday precision, CV were < or =10% and accuracy ranged from 90 to 102%. This method is specific, sensitive, reproducible, and practical in a clinical setting.

Calibration↗
PubMed1972

Automated slide staining machine.

A machine is described which can perform the Gram stain. Comparison of slides stained by machine versus hand revealed no difference in reproducibility or accuracy. In addition to providing clean, dry, uniformly stained slides, the machine saves 24 sec per slide when compared with a hand staining technique.

Acetone↗