Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: C35E7 .10
 63,145 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The initial stage of atherosclerotic plaque formation involves oxidation of the phosphatidyl-choline moiety of low density lipoprotein (LDL) and subsequent uptake by macrophages. Ongoing uptake in developing plaque also may involve oxidized LDL and would require an oxidizing environment in plaque lipids. Atherosclerotic plaque lipids from 12 patients undergoing peripheral vascular procedures were extracted in chloroform: methanol (2:1). This extract was applied to a 25 cm 5 micron silica HPLC column and eluted with a ternary gradient mobile phase utilizing a laser light scattering (ELSD) mass detector. Individual lipid fractions were then analyzed. Cholesterol, both free and esterified, was the most prominent lipid in plaque (104 +/- 74 mg/gm tissue. However, lipid peroxides were present in much higher concentrations (3.52 +/- 2.84 FU X 10(4)/mg phospholipid) and overall level (21.27 +/- 10.10 FU X 10(4)/gm plaque) in the phospholipid component (*p< 0.05). Phosphatidyl-choline (PC) accounted for 63% of the total phospholipid peroxides recovered (6.31 +/- 5.09 mg/gm plaque; *p<0.05). PC and phosphatidylinositol (PI) content were linearly related to lipid peroxide fluorescence (PC; r=0.696; p=0.01) (PI; r=0.809; p=0.001). Lipid peroxides in human atherosclerotic plaque are present primarily in the phospholipid component and phosphatidyl-choline forms the bulk of these peroxides. PC may play an important role in ongoing plaque lipid accumulation.
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PMID:Mature human atherosclerotic plaque contains peroxidized phosphatidylcholine as a major lipid peroxide. 863 20

A simple and rapid liquid chromatographic (LC) method has been developed for simultaneous determination of 9 pyrethroid insecticides (biphenthrin, cypermethrin, fenpropathrin, fenvalerate, flucythrinate, methothrin, permethrin, py-115, and tetramethrin) in fruits and vegetables. Residues are extracted from crops with methanol and partitioned with toluene. Extracts are cleaned up by Florisil-charcoal column chromatography. LC separation is performed on a muBondapak C18 stainless steel column with acetonitrile-deionized water as mobile phase. The insecticides are detected at 206 nm with 0.03 absorbance unit full scale. Recoveries of 9 pyrethroid insecticides from 6 crops (cucumbers, tomatoes, cabbages, apples, pears, and peaches) fortified at 0.5-5.0 mg/kg were 62.7-129.2%. Detection limits were about 0.05 mg/kg, except for py-115, for which detection limit was 0.10 mg/kg.
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PMID:Multiresidue liquid chromatographic method for simultaneous determination of pyrethroid insecticides in fruits and vegetables. 866 85

A facile, sensitive and highly specific HPLC method for assaying 1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU) in plasma has been developed. The drug was efficiently isolated from plasma by extraction with tert.-butyl methyl ether. A structurally related compound with similar physicochemical properties served as the internal standard (I.S.). Following evaporation of the organic solvent, the extract was reconstituted with 0.05 M ammonium acetate buffer, pH 5.0, and loaded onto a 4 micron Nova-Pak C18 column (15 cm x 3.9 mm), which was preceded by a 7 micron Brownlee RP-18 precolumn (1.5 cm x 3.2 mm). Chromatography was performed at ambient temperature using a mobile phase of methanol-0.1 M ammonium formate buffer, pH 3.7 (25:75, v/v). UV absorbance of the effluent was monitored at 240 nm. A flow-rate of 1.0 ml/ min was used for analyzing mouse and dog plasma extracts. Under these conditions, the drug eluted at 4.0 min and was followed by the I.S. at 6.1 min. An automatic switching valve was employed to allow the precolumn to be flushed 1.5 min into the run, without interrupting the flow of the mobile phase to the analytical column, thereby preventing the apparent build-up of extractable, strongly retained, UV-absorbing components present in mouse and dog plasma. Operating in this manner, more than 100 samples could be analyzed during a day using a refrigerated autosampler for overnight injection. The method was readily adapted to the determination of SarCNU in human plasma by simply decreasing the eluent flow-rate to 0.6 ml/min, whereby SarCNU and the I.S. eluted at approximately 5.8 and 9.1 min, respectively. Furthermore, the switching valve was not necessary for the analysis of human plasma samples. With a 50-microliter sample volume, the lowest concentration of SarCNU included in the plasma standard curves, 0.10 micrograms/ml, was quantified with a 7.8% R.S.D. (n = 27) over a 2 month period. Plasma standards, with concentrations of 0.26 to 5.1 micrograms/ml, exhibited R.S.D. values ranging from 1.3 to 4.7%. Thermospray-ionization MS detection was used to definitively establish the specificity of the method. The sensitivity of the assay was shown by application to be more than adequate for characterizing the plasma pharmacokinetics of SarCNU in mice.
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PMID:Specific high-performance liquid chromatographic assay with ultraviolet detection for the determination of 1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea in plasma. 870 41

A sensitive reversed-phase high-performance liquid chromatographic fluorescence method is described for the simultaneous determination of topotecan (I) and the hydrolysed lactone ring-opened product hydroxy acid (II) in plasma and for the determination of I in urine. To 250 microliters of plasma, a 750-microliters volume of cold methanol was added to stabilize the pH-dependent conversion of I into II. In plasma, the lower limit of quantitation (LLQ) for both compounds was 0.10 ng/ml. The between-day variation for I at the LLQ was 7.1% and for II was 5.5%. Prior to injection, urine samples were acidified with orthophosphoric acid and diluted with phosphate-buffered saline (PBS). In urine, the calibration curve for I was linear in the range of 10 to 250 ng/ml and the LLQ was 10 ng/ml. The assay was developed to enable pharmacological analysis of I, in on-going phase I and II studies, in patients with solid tumors.
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PMID:Sensitive high-performance liquid chromatographic fluorescence assay for the quantitation of topotecan (SKF 104864-A) and its lactone ring-opened product (hydroxy acid) in human plasma and urine. 873 36

Hair analysis for drugs of abuse provides a possible long-term measure of drug use not possible with urinalysis. Many drugs and their metabolites have been detected in hair; however, the factors influencing the incorporation of chemicals into hair are poorly understood. An animal model for chemical uptake into hair utilizing controlled drug administration was developed to ascertain if increasing doses of codeine are reflected in the concentrations of codeine and its metabolites found in hair. Male Sprague-Dawley rats were administered codeine at 5, 10, or 20 mg/kg (intraperitoneally; n = 6) daily for 21 days. At various times during and after the dosing protocol, approximately 50 mg of hair was shaved from a different area of the animals' backs and analyzed for codeine and morphine concentrations by ion-trap gas chromatography-mass spectrometry. Peak hair codeine concentrations for the 5-, 10-, and 20-mg/kg groups occurred 20 days after beginning the dosing protocol and were 0.57 +/- 0.13, 0.80 +/- 0.10, and 1.95 +/- 0.35 ng/mg hair, respectively. Morphine peak concentrations occurred at the same time and were 1.08 +/- 0.28, 1.21 +/- 0.09, and 2.10 +/- 0.26 ng/mg hair for the 5-, 10-, and 20-mg/kg groups, respectively. Long-term dosing in the rat resulted in similar or greater hair concentrations of morphine (metabolite) than codeine. The plasma pharmacokinetics of codeine and morphine were also obtained after a single, intraperitoneal codeine administration of 20 mg/kg. An experiment involving washing the rat hair with methanol or phosphate buffer (pH 9.0) did not reduce the concentration of codeine or morphine measured in hair as compared with nonwashed control hair. Data obtained in this study indicate that after controlled administration the incorporation of codeine and its metabolite, morphine, into rat hair occurs in a distinct dose-proportional manner.
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PMID:Distribution of codeine and morphine into rat hair after long-term daily dosing with codeine. 892 32

A sensitive high performance liquid chromatographic (HPLC) assay has been developed and validated for the quantitation of the novel anticancer agent topotecan and topotecan as its lactone plus carboxylate forms in rat and dog plasma. Linear responses in analyte standard peak areas were observed over the concentration ranges 0.10-10 ng ml-1 using 100 microliters of rat plasma and 0.2-100 ng ml-1 using 100 microliters of dog plasma. Due to the instability of the drug in the biological matrix it was necessary to obtain the plasma fraction within 5 min after blood sampling by centrifugation, immediately followed by protein precipitation with cold methanol (-30 degrees C). For the determination of total drug levels (lactone plus lactone ring-opened form), plasma samples were deproteinated with methanol and subsequently acidified with 2% (v/v) perchloric acid. The samples were analysed by HPLC using a Zorbax SB-C18 Stable Bond column and methanol-0.1 M hexane-1-sulfonic acid in methanol-0.01 M N,N,N'N'-tetramethylethylenediamine in distilled water pH 6.0 (25:10:65, v/v/v) as the mobile phase. The detection was performed fluorimetrically. The analytical column was thermostated at 19-21 degrees C to obtain baseline resolution between an interfering endogenous compound in rat and dog plasma and topotecan. This endogenous peak was absent in human plasma. Variation of chromatography temperature appeared to be a very useful tool in the bioanalysis of topotecan. It allowed optimization of the separation between the endogenous compound and the analyte; different mechanisms of solute interactions are apparently involved in this reversed-phase ion-pair chromatographic system.
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PMID:The impact of column temperature in the high performance liquid chromatographic analysis of topotecan in rat and dog plasma. 893 30

A high-performance liquid chromatographic (HPLC) method was developed which involves the use of two 5-microns BDS silica gel columns (15 cm x 4.6 mm I.D.) in series for increased resolution and sensitivity, and an organic mobile phase for both extraction and elution of diltiazem. Plasma samples (400 microliters) were extracted using the organic mobile phase [n-hexane-methanol-dichloromethane-ammonia (370:35:30:0.3)] and the extracts were monitored at 240 nm. Desipramine (30 micrograms ml-1) was the internal standard. The limit of quantification in plasma was 20 ng ml-1 with a correlation coefficient of > or = 0.999 within the 20-800 ng ml-1 standard window. The inter- and intra-assay R.S.D.s were within 5%. The recovery of diltiazem varied from 101.1% at 20 ng ml-1 to 93.7% at 400 ng ml-1. The method was applied to the investigation of diltiazem absorption in a rat. Drug absorption was based on the intestinal single-pass perfusion model. The concentration of diltiazem in all test perfusion solutions was 1 mg ml-1 (2.4 mM) and the flow-rate through the system was 3.33.10(-3) ml s-1. A non-specific mucolytic absorption enhancer was also added to a diltiazem solution and studied in the in situ system. The pharmacokinetics of diltiazem hydrochloride were investigated in two study groups of Wistar rats (n = 4). A two-sample Student's t-test was employed to compare values of the area under the curve (AUC). The pharmacokinetic data indicated that the AUC in the group which received the enhancer [18.12 +/- 5.43 ng ml-1 h-1 (+/- S.D.)] was higher than that in the control group (11.49 +/- 3.67 ng h-1 ml-1), t-test; p = 0.0483. Hence it was shown that administration of an enhancer could increase the oral bioavailability of diltiazem.
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PMID:High-performance liquid chromatographic assay for diltiazem in small-volume blood specimens and application to pharmacokinetic studies in rats. 900 53

Doxepin is a tricyclic antidepressant marketed as an irrational mixture of cis- and trans-geometric isomers in the ratio of 15:85. A convenient high-performance liquid chromatographic (HPLC) procedure for simultaneous quantitation of geometric isomers of doxepin and N-desmethyldoxepin in plasma and urine is described. The HPLC procedure employed a normal phase system with a silica column and a mobile phase consisting of hexane-methanol-nonylamine (95:5:0.3, v/v/v), a UV detector and nortriptyline as the internal standard. The liquid-liquid extraction solvent was a mixture of n-pentane-isopropanol (95:5, v/v). The limit of quantitation was 1 ng/ml for each isomer. The calibration curves were linear over the ranges 1-200 ng/ml (plasma) and 1-400 ng/ml (urine). In plasma, the accuracy (mean +/- S.D.) (97.53 +/- 1.67%) and precision (3.89 +/- 1.65%) data for trans-doxepin were similar to corresponding values for urine, i.e., 97.10 +/- 2.40 and 3.82 +/- 1.14%. Accuracy and precision data for trans-N-desmethyldoxepin in plasma were 97.57 +/- 2.06 and 4.38 +/- 3.24%, and in urine were 97.64 +/- 3.32 and 5.26 +/- 1.83%, respectively. Stability tests under three different conditions of storage indicated no evidence of degradation. The recovery of doxepin was 61-64% from plasma and 63-68% from urine. The method has been applied to analyses of plasma and urine samples from human volunteers and animals dosed with doxepin.
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PMID:Stereoselective and simultaneous measurement of cis- and trans-isomers of doxepin and N-desmethyldoxepin in plasma or urine by high-performance liquid chromatography. 914 Jul 66

The mechanism by which n-alkanols produce anesthesia and the characteristics relevant to those mechanisms (e.g., lipid solubilities versus potencies) remain unknown. Accordingly, we determined potencies (minimum alveolar anesthetic concentration [MAC]) and solubilities of normal methanol, ethanol, butanol, hexanol, and octanol. We also determined the additivity of these alkanols with a conventional anesthetic (desflurane) and the additivity of methanol with butanol. Finally, we determined whether alkanol metabolism influences alkanol potencies. MAC for methanol, ethanol, butanol, hexanol, and octanol (0.00200, 0.000989, 0.000133, 0.0000214, and 0.00000117 atm, respectively) increased with an increasing solubility in olive oil (olive oil/gas partition coefficients 48.6, 108, 1,650, 11,600, and 93,500, respectively) and octanol (octanol/gas partition coefficients 163, 1,150, 22,900, 135,000, and 4,140,000) to give a product of MAC x solubility for olive oil approximately 10 times less (values of 0.10-0.25) than that expected from the Meyer-Overton hypothesis (compared with conventional inhaled anesthetics). There was less deviation for octanol, but the results were more variable. Inhibition of methanol and butanol metabolism by 4-methylpyrazole did not alter MAC. Methanol, ethanol, butanol, hexanol, and octanol had approximately additive anesthetic effects with desflurane, with some small but statistically significant deviations both above and below additivity. In the presence of 0.5 MAC of desflurane, we needed to add 0.4-0.6 MAC of each alkanol to inhibit the movement of 50% of the rats in response to noxious stimulation. Similarly, the effects of methanol and butanol were additive (with each other). The saline/gas partition coefficient for each alkanol was high (3700, 2650, 1400, 900, and 709 for methanol through octanol), which indicates high polarity. We conclude that the potent anesthetic effects of normal alkanols may result from an affinity to both polar and nonpolar phases. Our finding of additivity of alkanols with each other is consistent with a common mechanism of action. Similarly, the finding of additivity or slight deviations from additivity for alkanols with desflurane is consistent with mechanisms of action that have much in common.
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PMID:Anesthetic potencies of n-alkanols: results of additivity and solubility studies suggest a mechanism of action similar to that for conventional inhaled anesthetics. 914 29

A rapid, simple and reliable liquid chromatographic method has been developed for the simultaneous determination of nicotinamide, thiamin, riboflavin, pyridoxine, pyridoxal, pyridoxamine, cyanocobalamine and folic acid in liquid and powdered infant milk. Ion-pair chromatography with a reversed-phase C18 column is used. Six vitamins were resolved in a single analysis; total analysis time never exceeded 55 min. A mobile phase of methanol-water (15:85), 5 mM octanesulfonic acid, with 0.5% triethylamine at pH 3.6 and a flow-rate of 1.0 ml/min gave the most satisfactory separation of these vitamins using a UV detector set at different wavelengths. Sample preparation involves acidification to precipitate proteins, and centrifugation followed by gravity filtration. Linearity, precision, recovery and sensitivity were always satisfactory. Detection limits ranged from 0.02 to 0.10 microgram/ml and determination limits ranged from 0.03 to 0.25 microgram/ml.
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PMID:Determination of water-soluble vitamins in infant milk by high-performance liquid chromatography. 929 39


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