Gas chromatographic--mass spectrometric determination of haloperidol in plasma. Application to pharmacokinetics

An improved gas chromatographic-mass spectrometric chemical ionization assay for the quantitative determination of haloperidol in body fluids is presented. A fused silica, bonded phase capillary column, combined with negative ion chemical ionization (NICI), ammonia as a selective reagent gas and the monitoring of preselected characteristic ions (SIM), provide the combined sensitivity and selectivity necessary for reliable measurements in the low ng/ml range. The lower limit of detection was 0.1 ng/ml plasma and the calibration curve linear in the measured range of 0.1-5 ng/ml. In combination with the excellent imprecision and inaccuracy data and a recovery exceeding 90%, the method is very well suited for quantitative determinations of plasma samples generated during clinical studies, e.g. evaluating the pharmacokinetics and/or bioavailability/bioequivalence of haloperidol.     

Validation of a liquid chromatographic tandem mass spectrometric method for the determination of sumatriptan in human biological fluids

A liquid chromatographic tandem mass spectrometric method for the quantitative determination of sumatriptan base in human plasma and urine has been developed and validated over the concentration range 0.2–20 ng base ml⁻¹. Sumatriptan is a 5-HT₁ receptor agonist which has found widespread use in the treatment of migraine. Sumatriptan and its internal standard (D₃-sumatriptan) were extracted from human matrices using C₂ solid phase cartridges. The extracts were chromatographed on a C₁₈ column, ionised using a heated nebuliser assisted atmospheric pressure ionisation (API) interface and detected by MS/MS in the multiple reaction monitoring mode. The completed validation demonstrated the method to be robust, accurate, precise and specific for the direct quantification of sumatriptan in human fluids. The method was used on a routine basis to determine the levels of sumatriptan in human volunteers following the oral administration of a 25 mg dose of sumatriptan succinate.     

Gas chromatographic — Mass spectrometric determination of dixyrazine in human blood

Summary A gas chromatographic — mass spectrometric method for the determination of dixyrazine in plasma has been developed. The method was found to offer high specificity, sensitivity, accuracy and precision and should be adequate for analysis of dixyrazine kinetics in man. There appeared to be great inter-individual variation in the disposition of the drug.Deceased     

Gas chromatographic determination and pharmacokinetics of 4-hydroxybutyrate in dog and mouse

A rapid and reproducible method was developed to extract 4-hydroxybutyrate from plasma as 4-butyrolactone for subsequent gas chromatographic (GLC) assay. The drug, an intravenous anesthetic and oral hypnotic in man, was infused into four dogs and the plasma concentration was determined by ¹⁴ C-isotope dilution and GLC. Pharmacokinetic parameters for distribution and elimination were calculated. A capacity-limited process appears to be involved in the elimination of 4-hydroxybutyrate in the dog. Macroautoradiography revealed the distribution pattern in normal and pregnant adult mice.     

Gas chromatographic/mass spectrometric determinations of indomethacin serum levels in the course of pharmacokinetic studies in healthy volunteers

For 4 different brands of indomethacin preparations the in vitro dissolution data as well as their relative bioavailabilities were determined. The in vitro tests were performed by the rotating basket method; the quantitative determinations of the serum-levels were determined by an gas chromatographic/mass spectrometric assay employing registration of the characteristic selected ion current profiles of the compound. Furthermore a special method for synthesis of the needed internal standard was also developed. The in-vivo-studies - with 15 volunteers in a 4 fold crossover-showed - in contrast to the worse in-vitro-dissolution of one preparation - bioequivalency of all four preparations. Our results clearly show that statements on in-vitro/in-vivo correlations have to be cautious.     

生物样品中莱曼宁的气相色谱测定及其在动物体内的药代动力学

本文采用气相色谱法分离并测定了生物样品中莱曼宁的浓度,研究了莱曼宁在动物体内的吸收、分布和排泄过程。小鼠ig莱曼宁后的吸收速率常数为0.73h~(-1)。大鼠4h的胆汁排泄量仅为给药量的0.6％,大鼠尿中32h排泄量为给药量的13.3％。大鼠iv给药后体内过程符合二房室特征。大鼠体内分布以肾脏最高,其次为脾、肝、心、脑,外周组织如脂、肌含量较少。莱曼宁与兔血浆蛋白的结合率为49.2％。     

High performance liquid chromatography-tandem mass spectrometric determination of rupatadine in human plasma and its pharmacokinetics

A simple, rapid, sensitive and selective liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the quantification of rupatadine in human plasma using estazolam as internal standard (IS). Following liquid-liquid extraction, the analytes were separated using a mobile phase of methanol-ammonium acetate (pH 2.2; 5mM) (50:50, v/v) on a reverse phase C18 column and analyzed by a triple-quadrupole mass spectrometer in the positive ion and multiple reaction monitoring (MRM) mode, m/z 416-->309 for rupatadine and m/z 295-->267 for the IS. The assay exhibited a linear dynamic range of 0.1-100 ng/ml for rupatadine in human plasma. The lower limit of quantification (LLOQ) was 0.1 ng/ml with a relative standard deviation of less than 20%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The validated LC-MS/MS method has been successfully applied to study the pharmacokinetics of rupatadine in healthy volunteers.     

Thin-layer and gas-liquid chromatographic procedures for the determination of perazine and its metabolites in human body fluids.

The quantitative determination of perazine, a neuroleptic drug, and its metabolites in body fluids is difficult in view of the low concentrations to be expected under therapeutic conditions as well as of the problem of convenient detectors. Different methods for extraction and measurement of perazine concentration in blood samples are discussed, with special consideration of partition coefficients and the properties of the chromatographic systems (thin-layer and gas-liquid chromatography). A new and simple method for rapid gas chromatographic determination of perazine is presented.     

A gas chromatographic mass spectrometric assay for the determination of aphidicolin in plasma of cancer patients

A gas chromatographic-mass spectrometric (GC-MS) method is described for the determination of the novel anticancer agent aphidicolin in plasma. The extraction was carried out in a solvent mixture of hexane:isopropanol (10:1) and the external standard aphidicolane was added after evaporation of the organic phase. The residue was then redissolved in a derivatizing mixture containing bis(trimethylsilyl)trifluoracetamide as sililating agent, pyridine, and trimethylchlorosilane, and allowed to react at 80 degrees C for 2 h. After GC separation of the derivatized samples, selected ion recording analysis was done, monitoring the ions at mass 523.3 and 448.3 for aphidicolin and aphidicolane, respectively. The mean recovery +/- SD of aphidicolin from plasma was 73.5 +/- 11.6% in the range from 5 to 800 ng. This method was applied to determine aphidicolin plasma levels in three cancer patients in Phase I clinical trials of aphidicolin-17-glycinate administered as a 1-h iv infusion. Two patients received dose of 290 mg/m2 and the third received 435 mg/m2. Aphidicolin plasma levels at the end of infusion were very low, and the drug rapidly disappeared from plasma with a terminal (beta) half-life of 2 h.     

Application of a liquid chromatographic/tandem mass spectrometric method to a kinetic study of derivative glucosamine in healthy human urine

A sensitive, selective and efficient liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method was developed and validated for the determination of glucosamine in healthy human urine. Urine samples were extracted by acetonitrile and derivatized with o-phthalaldehyde/3-mercaptopropionic acid. Analysis was then carried out using ESI source and methanol/0.2% ammonium acetate-0.1% formic acid mobile phase gradient elution, with tolterodine tartrate as the internal standard. The linear calibration curve ranged from 0.41μg/ml to 82.7μg/ml. The intra-day and inter-day precisions were less than 3.93% and 10.0%, respectively. The extraction recoveries determined at three concentration levels were higher than 88.6%. The method was successfully applied for determining the urine concentration of glucosamine up to 24h after oral administration of 1g glucosamine sulfate dispersible table (containing 785.08mg glucosamine) from a clinical pharmacokinetic study in healthy volunteers.     

A rapid chromatographic/mass spectrometric method for digoxin quantification in human plasma

The relatively simple liquid-liquid extraction LC-MS/MS method using a UPLC column for measurement of digoxin concentrations both in medium and human plasma is described. Digitoxin was used as internal standard. The developed method possesses satisfactory accuracy, precision, and repeatability, and is economical and not time-consuming. It is the first method for precise measurement of digoxin concentrations in human plasma using combined HPLC equipment and UPLC column with a low limit of quantitation equal to 0.1 ng ml ^{– 1} as verified in more than 1500 samples analyzed in a GCP GLP bioequivalence study. The developed method was successfully used in digoxin bioequivalence studies in which 26 volunteers were enrolled.     

Gas chromatographic determination of prostaglandins

Progress in separation and detection of prostaglandins and the other metabolites of arachidonic acid by means of GC-ECD, GC-MS, and GC-MS-MS in the course of the past fifteen years was reviewed. One discussed the problems of sample preparation, selection of proper chromatographic conditions, and detection modes available. Finally, applications of the methods developed to detection and quantification of prostanoids in biological material was presented.     

液相色谱-电喷雾电离质谱法检测地高辛人血浆药物浓度方法学的建立与考证

目的:建立适用于地高辛临床血药浓度监测的液相色谱-电喷雾电离质谱方法(LC-ESI-MS)。方法:地高辛人血浆样本采用乙酸乙酯液液萃取后以LC-ESI-MS方法进行分析。采用Kro-masilC18柱(150mm×2.00mm,3.5μm)分析柱;在乙腈和氯化铵的混合流动相的流动相系统中,进行梯度洗脱,选择性负离子检测,地高辛m/z为815.40,内标Rg2m/z为819.00。结果:地高辛在0.05～10.0ng/mL浓度范围内线性关系良好(r=0.9989),血浆内杂质不影响药物的检测,方法回收率大于75%,批内、批间变异均小于15%,冻融稳定性良好。结论:本研究所建立的LC-ESI-MS测定方法操作简便、快速、灵敏,准确,重现性好,所需血浆量少,可用于地高辛临床血药浓度监测及临床药动学研究。