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%.
In-process control of midazolam synthesis by HPLC.
A high-performance liquid chromatographic assay coupled with UV detection (239 nm) has been developed for the determination of midazolam and its synthesis precursors. The separation of the analytes was performed on a Kromasil C8 column (15 cm x 4.6 mm i.d., 5 microm) at 30 degrees C. The mobile phase [ammonium chloride (pH 5.5, 1 g l(-1))-methanolacetonitrile (45:22:33, v/v/v)] was pumped at a flow-rate of 1.5 ml min(-1). This method is rapid (less than 11 min), sensitive (limit of detection (LOD) ranged between 0.05 and 0.5 mg l(-1)) and selective for the determination of midazolam, and it could be used for monitoring different synthetic routes.
Growth from Solutions
Growth from solutions is the crystallization of a compound whose chemical composition differs markedly from that of the initial liquid phase. Commonly used solvents are water, multicomponent aqueous or nonaqueous solutions, and melts of some chemical compounds. Differentiations are made based on growth temperatures and on the chemical nature of the solvent. In growth from low-temperature aqueous solutions, the temperatures generally do not exceed 80–90°C; in growth from superheated aqueous solutions (hydrothermal method), they reach 800°C, and in growth from salt melts (molten-salt, flux, or fluxed melt growth), they usually do not exceed 1200–1300°C, but sometimes reach 1500°C.