QUANTIFICATION OF THE NEUROMUSCULAR BLOCKING-AGENT ROCURONIUM AND ITSPUTATIVE METABOLITE 17-DESACETYLROCURONIUM IN HEPARINIZED PLASMA BY CAPILLARY GAS-CHROMATOGRAPHY USING A NITROGEN SENSITIVE DETECTOR

We have developed a sensitive and specific capillary GC (cGC) assay fo r the quantification of the quarternary aminosteroidal compound rocuro nium (roc), a neuromuscular blocking agent, and its putative metabolit e 17-desacetylrocuronium (17OH-roc), using 3-desacetylvecuronium (3OH- vec) as an internal standard (I.S.). This novel method has been applie d to a pharmacokinetic study with roc, monitoring sixty patients who w ere classified according to four different body mass index (BMI) group s. The isolation of these drugs from plasma was carried out using a di chloromethane liquid-liquid extraction after ion-pairing of the positi vely charged ammonium compounds with iodide. To achieve thermal stabil ity, tert.-butyldimethylsilyl-ethers were formed at the 3OH- and 17OH- steroidal positions by reaction with yl-N-(tert.-butyldimethylsilyl)-t rifluoroacetamide at 70 degrees C overnight. An automated cGC system f itted with a nitrogen sensitive detector with a specially prepared gla ss phase bead and a computer controlled data handling system was used to analyze and quantify the compounds, which were separated on a DB1 c apillary column with helium as the carrier gas and a temperature progr am ranging from 120 to 300 degrees C. The method is linear for 50-6400 ng/ml for roc and 80-6400 ng/ml for 17OH-roc. The detection limits we re 10 ng/ml for roc and 50 ng/ml for 17OH-roc. The lower limit of quan tification was 50 ng/ml for roc and 80 ng/ml for 17OH-roc. Intra-assay coefficients of variation (C.V.s) were 10% and 15% and the inter-assa y C.V.s 8-18% and 16-21% for roc and 17OH-roc, respectively. (C) 1997 Elsevier Science B.V.