The determination of total and unbound midazolam in human plasma. A comparison of high performance liquid chromatography, gas chromatography and gas chromatography/mass spectrometry.
Midazolam concentrations in patients' plasma was determined after extraction with high performance liquid chromatography (HPLC), gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). GC was selected for routine plasma assays in terms of selectivity, simplicity, precision, accuracy and sensitivity (0.02 microgram/mL); HPLC analysis was less sensitive (0.1 microgram/mL) than GC; GC/MS was used for analysis validation. Plasma protein binding of midazolam was determined by GC in patients' plasma after in vitro incubation with midazolam, ultrafiltration and extraction; 5% of the drug was unbound to plasma proteins. Midazolam distribution in lipoprotein fractions separated by ultracentrifugation of plasma obtained from patients on prolonged midazolam treatment was also assayed by GC.
de Vries
J X
JX
Abteilung für Klinische Pharmakologie, Medizinische Klinik der Universität, Heidelberg, FRG.
Rudi
J
J
Walter-Sack
I
I
Conradi
R
R
D001798:Blood Proteins / Q000378:metabolism; D002849:Chromatography, Gas / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D008874:Midazolam / Q000097:blood*; D011485:Protein Binding
D001798:Blood Proteins; D008874:Midazolam