Gas chromatographic determination of midazolam in low-volume plasma samples.
A gas chromatographic method for the sensitive determination of midazolam in plasma volumes as low as 40 microliters was developed, utilizing clinazolam as the internal standard. After liquid-liquid extraction at basic pH into 1-chlorobutane-dichloromethane (96:4) a 2- to 4-microliters portion of the reconstituted extract was injected under electronic pressure control onto a 12 m x 0.2 mm I.D. methyl silicone capillary column, and was exposed to a three-step temperature program from 120 to 310 degrees C, to separate the analytes from the plasma constituents. The compound of interest was identified and quantified by means of a mass-selective detector. The assay was linear from 10 to 500 ng/ml using 40 microliters of plasma (limit of quantification: 10 ng/ml) and was linear from 0.25 to 100 ng/ml using 500 microliters of plasma (limit of quantification: 0.25 ng/ml). The intra-day precision for the 40-microliters aliquots varied from 2.2 to 6.6%, the corresponding accuracy from -7.4 to -4.4%; the inter-day precision ranged from 5 to 7.2% and the corresponding accuracy from -7.2 to -5.1%.
Podkowik
B I
BI
Department PRPK, F. Hoffmann-LaRoche Ltd., Basel, Switzerland.
Masur
S
S
D000759:Adjuvants, Anesthesia / Q000097:blood*; D000818:Animals; D002849:Chromatography, Gas / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006993:Hypnotics and Sedatives / Q000097:blood*; D008832:Microchemistry; D008874:Midazolam / Q000097:blood*; D051381:Rats; D012680:Sensitivity and Specificity
D000759:Adjuvants, Anesthesia; D006993:Hypnotics and Sedatives; D008874:Midazolam