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Biomedical subjects

C A Lau-Cam

Publications and source records attributed to C A Lau-Cam.

At least 19 recordsLinked to original sources
PubMed2001

Monohydroxylation and esterification as determinants of the effects of cis- and trans-9-octadecenoic acids on the permeation of hydrocortisone and 5-fluorouracil across hairless mouse skin in vitro.

The effects of cis-9-octadecenoic acid (oleic acid) and of a group of chemically related cis- (ricinoleic acid) and trans- (ricinelaidic acid) 12-monohydroxylated derivatives and their corresponding ethyl and methyl esters on the skin permeation of model hydrophobic (hydrocortisone, log K=1.61) and hydrophilic (5-fluorouracil, log K=-0.89) drugs was investigated in vitro using excised hairless mouse skin. Drug solutions were prepared in propylene glycol, with and without the addition of a fatty acid to a level of 5%. Whereas the addition of oleic acid markedly enhanced the transdermal flux of both drugs relative to a sample in propylene glycol alone (hydrocortisone approximately 1800-fold; 5-fluorouracil approximately 330-fold), that of a cis- or trans-12-monohydroxylated analog of oleic acid resulted in only a small increase (1.4-2.7-fold for hydrocortisone; 4.4-6.6-fold for 5-fluorouracil). On the other hand, the methyl and ethyl esters of cis- and trans-12-hydroxy-9-octadecenoic acid exerted a much greater enhancing effect (327-720-fold for hydrocortisone, 42-74-fold for 5-fluorouracil) than the corresponding parent fatty acids. Furthermore, whereas the ethyl esters were found to have a greater effect on the skin permeation of hydrocortisone than the methyl esters, the reverse was true with regards to 5-fluorouracil. Additionally, the esters of trans-12-hydroxy-9-octadecenoic acid promoted permeation to an extent comparable to that achieved with their cis-counterparts.

Animals↗
PubMed2001

A simple method for the identification and assay of iopamidol and iothalamate meglumine in pharmaceutical samples based on proton nuclear magnetic resonance spectroscopy.

A proton nuclear magnetic resonance (PMR) spectroscopic method is described for the direct assay and identification of the triiodinated radiographic contrast agents iopamidol (nonionic type) and iothalamate meglumine (ionic type) in commercial solutions and as a bulk material. Samples were prepared by simply diluting an injectable solution with or dissolving a powdered sample in D2O. Sodium acetate was added to serve as an internal standard. Quantitations were based on the resonance signals for the protons of the CH3-CO-group at 1.58 ppm (iopamidol) or 2.25 ppm (iothalamate), CH3-N-group at 2.38 ppm (meglumine) and CH3-CO-group at 1.92 ppm (acetate). The mean +/- SD (n = sets of 10 samples each) recovery of iopamidol, iothalamic acid and meglumine from synthetic mixtures with the internal standard were 99.6 +/- 0.63, 99.7 +/- 0.66 and 99.9 +/- 1.18%, respectively; with the values ranging from 98.7-100.9% for iopamidol and iothalamate, and from 98.3-100.8% for meglumine.

Contrast Media↗
PubMed2001

A stability-indicating proton nuclear magnetic resonance spectroscopic method for the analysis of propantheline bromide in pharmaceutical samples.

A rapid, specific and accurate proton nuclear magnetic resonance (1H NMR) spectroscopic method was developed for the simultaneous quantitative analysis of propantheline bromide and its degradation product, xanthanoic acid, in bulk materials and tablets. 1,3,5-Trinitrobenzene served as an internal standard and deuterochloroform was used as the solvent for the analytical samples. The quantities of propantheline bromide and xanthanoic acid were calculated on the basis of the integrals for signals of the methine proton of propantheline at 5.09 ppm, the methine proton of xanthanoic acid at 4.99 ppm, and the aromatic protons of the internal standard at 9.39 ppm. The accuracy of the method was established through the analysis of synthetic mixtures containing the parent compound, its degradation product and the internal standard. An excellent agreement was verified between the assay results and the quantities of the various compounds in the mixtures. The mean +/- SD recovery values for propantheline bromide and xanthanoic acid from a set of 10 synthetic mixtures were 99.6 +/- 0.8% and 98.9 +/- 1.8%, respectively. The assay of 10 lots of commercial propantheline bromide tablets by 1H NMR spectroscopy indicated drug and degradate contents in the ranges 97.1-99.8% and 0.1-0.9%, respectively. In addition, the proposed analytical method was found suitable for detecting the formation of xanthanoic acid from propantheline bromide in aqueous media in concentrations below 0.1% of that of the parent compound.

Drug Stability↗
PubMed1999

Evaluation of the effect of polyethylene glycol 400 on the nasal absorption of nicardipine and verapamil in the rat.

This study has investigated the effect of polyethylene glycol (PEG) 400 on the intranasal absorption and ensuing pharmacokinetics of the calcium entry blockers nicardipine and verapamil in a rat model. To solutions of nicardipine in acetate buffer pH 5.0 and of verapamil in distilled water, PEG 400 was added in concentrations of 0-5%. The nasal bioavailability of nicardipine from plain buffered solution was 44%, and increased steadily to 56-79% in direct proportion to the amount of PEG 400 added. Verapamil, on the other hand, exhibited an intranasal bioavailability of 52% in the absence of PEG 400, and between 61-68% in the presence of increasing concentrations of PEG 400. None of the formulations tested was found to cause adverse effects on the morphology and integrity of the nasal mucosa.

Administration, Intranasal↗
PubMed1998

Simplified reversed-phase HPLC method with spectrophotometric detection for the assay of verapamil in rat plasma.

A high-performance liquid chromatographic (HPLC) method was developed for the assay of verapamil in rat plasma. After deproteinization of the plasma sample with an acetonitrile-perchloric acid (8:2) mixture containing dextromethorphan, the internal standard, an aliquot of the supernatant was directly analyzed on a cyanopropylsilane column with methanol-acetonitrile-triethylamine acetate buffer (10:30:60) as the mobile phase and detection at 235 mm. At a flow rate of 1.5 ml min-1, a complete analysis was completed in less than 6 min. The method was linear for verapamil concentrations in the range 0.5-10 micrograms ml-1 (r = 0.9999). Recoveries for the same drug concentrations from spiked rat plasma ranged from 85.6-93.0% (n = 8). The mean RSD values for intraday and interday assay reproducibility (n = 3) were, in both cases, less than 0.9%. The limit of detectability was about 0.1 microgram ml-1. The method was found useful to monitor the plasma levels of verapamil in rats that had received this drug by the nasal, oral and intravenous routes of administration.

Animals↗
PubMed1995

Determination of the optical purity of timolol maleate by proton nuclear magnetic resonance spectroscopy with a chiral Pr(III) shift reagent.

A 1H NMR spectroscopic method with chiral shift chelate is presented for the determination of the optical purity of timolol maleate. Optimum experimental conditions were established by studying the interactions of solvents (CCl4, CDCl3), substrate concentration, and the type and concentration of chiral lanthanide chelate (Pr(hfc)3, Eu(hfc)3). Larger induced shift (delta delta) and enantiomeric shift difference (delta delta delta) values, and more detailed spectral differences were obtained with Pr(hfc)3 than with Eu(hfc)3. By monitoring the spectral changes of the resonance signals for the enantiomeric -C(CH3)3 protons, suitable conditions for quantitative determinations were found when 0.1 molar equivalents of Pr(hfc)3 were complexed with 0.074 M of substrate. Enantiomeric compositions were calculated from the relative intensities of the enantiomeric -C(CH3)3 proton resonances. Based on the analysis of six synthetic enantiomeric mixtures, the mean +/- SD recovery of (R)-(+)-timolol by the proposed method was 99.5 +/- 1.17% of the amount added.

Adrenergic beta-Antagonists↗
PubMed1993

Determination of the optical purity and absolute configuration of threo-methylphenidate by proton nuclear magnetic resonance spectroscopy with chiral solvating agent.

The direct determination of both the optical purity and absolute configuration of threo-methylphenidate has been accomplished in a simple, specific, and accurate manner by 1H-NMR spectroscopy. The enantiomeric resonances of threo-methylphenidate were effectively resolved in CDCl3 solution by the addition of the chiral solvating agents (R)-(-)- or (S)-(+)-2,2,2,-trifluoro-1-(9-anthryl)ethanol. Optical purities were determined on the basis of the intensities of the enantiomeric ester methyl proton resonances; the assignment of enantiomeric configurations was based on the relative field positions of these resonances and the examination of molecular models. The analysis of synthetic enantiomeric mixtures of threo-methylphenidate by the proposed NMR method resulted in assay values that agreed closely with the known quantities of each enantiomer in the mixtures tested. The mean +/- SD recovery value for the (2S,2'S)-(-)-threo-enantiomer, amounting to 99.9 +/- 0.6% of added (n = 10), correlated well with that previously found by 1H-NMR spectroscopy with a chiral Eu(III) shift reagent. However, the present approach is simpler, shows less reliance on reagents and solvents of a high purity, and does not require strict anaerobic working conditions.

Magnetic Resonance Spectroscopy↗
PubMed1991

Instability of digoxin in digoxin-amorphous silicon dioxide triturates prepared by solvent deposition and ball milling.

Digoxin underwent hydrolytic degradation to its molecular components when solvent deposited on or ball milled with various commercial grades of amorphous silicon dioxide. The degradation was greater during ball milling than after solvent deposition, and increased with a longer ball milling. By itself digoxin was also degraded by ball milling, but not as much as when a silicon dioxide was present. The extent of the degradation appeared to depend on the acidity, surface area and pore size of the silicon dioxide used. A similar degradative behavior was observed for the related glycoside digitoxin.

Chemistry, Pharmaceutical↗
PubMed1991

Stimulation of rat liver glycogenolysis by vitamin B6: a role for adrenal catecholamines.

The administration of a single, 100-300 mg/kg ip, dose of a B6 vitamer to rats resulted in an almost immediate and gradual mobilization of the liver glycogen and a concomitant elevation of the serum glucose, with the order of potency being pyridoxal greater than pyridoxamine greater than pyridoxine. Since the B6 vitamer also stimulated the secretion of adrenal catecholamines and the accumulation of liver cAMP, and a pretreatment with selected blocking agents conferred significant protection against the glycogen depletion in the order of potency propranolol + phentolamine greater than propranolol greater than verapamil greater than phentolamine, a role for an adrenomedullary catecholamine-stimulated, beta-adrenoceptor-mediated, activation of the glycogen cascade system was suggested. This assumption was confirmed by verifying pyridoxal to possess virtually no effect on the liver glycogen of adrenalectomized rats.

Adrenal Medulla↗
PubMed1990

Optical purity determination of threo-methylphenidate hydrochloride using a chiral europium nuclear magnetic resonance (NMR) shift reagent.

A 1H-NMR spectroscopic method for the determination of the optical purity of threo-methylphenidate hydrochloride is presented. Complexation of the free-base form of the substrate with a chiral Eu(III) shift reagent resulted in two distinct enantiomeric ester methyl proton signals of utility for quantitative work. The accuracy of the method was validated by analyzing six synthetic mixtures of various proportions of (+)- and (-)-threo-methylphenidate. In addition to yielding assay results that were in close agreement with the known weights of each enantiomer in the mixture, and a mean recovery of the (-)-threo-enantiomer of better than 99.0%, the proposed method was capable of accurately measuring as little as 2% of one enantiomer in the presence of the other.

Europium↗
PubMed1990

Protection by pantethine, pantothenic acid and cystamine against carbon tetrachloride-induced hepatotoxicity in the rat.

The daily ip administration of pantethine (500 mg/kg), pantothenic acid (100 mg/kg) or cystamine (50 mg/kg) for 5 days conferred significant protection against the hepatotoxic and peroxidative actions of a 0.5 mL/kg ip dose of CCl4 in rats. All three treatments lessened the increases in serum ALT and liver TBARS values, and the reductions in serum triglyceride levels, and prevented the development of hepatic steatosis caused by the halocarbon. Pantethine was found to offer the greatest protection.

Alanine Transaminase↗
PubMed1989

Determination of the optical purity of indacrinone by proton nuclear magnetic resonance spectroscopy using chiral lanthanide chelates.

A simple, specific and reliable 1H-NMR spectroscopic method for the quantitative determination of the optical purity of indacrinone is described. After conversion of the S(+)- and R(-)-enantiomers to their methyl ester derivatives, they were coordinated with chiral europium(III) or praseodymium(III) shift reagents in CCl4/C2HCl3 (2:1). The optical purity was calculated from the relative intensities of the enantiomeric resonance signals for the protons of the methyl groups at position C(2) of the indanone ring. Mean +/- SD (n = 6) recoveries of S(+)-indacrinone from synthetic enantiomeric mixtures amounted to 99.75 +/- 0.63% when using europium(III) and 100.01 +/- 0.55% when using praseodymium(III).

Diazomethane↗
PubMed1986

General reversed-phase high-performance liquid chromatographic method for the separation of drugs using triethylamine as a competing base.

Triethylamine (TEA) was evaluated as a competing base for the retention control and peak shape improvement in the reversed-phase high-performance liquid chromatographic (RP-HPLC) analysis of selected acidic, basic, and neutral drugs. The effects of this amine on the capacity factor and theoretical plate number values of ephedrine, phenol, and sulfamerazine were examined on three unmodified commercial octadecylsilane chromatographic columns. Based on these results, a general RP-HPLC elution scheme using a mu Bondapak C18 10-micron column, methanol-acetic acid-TEA-water mobile phases, and an ultraviolet detector was developed for more than 150 drugs of pharmaceutical interest. The proposed method was applied to the separation of groups of chemically or pharmacologically related drugs that included sympathomimetic amines, antihistamines, phenothiazines, local anesthetics, Cinchona and tropane alkaloids, xanthines, sulfonamides, and steroids. In addition, paired-ion drugs such as physostigmine salicylate and combinations of ascorbic acid, benzoic acid, salicylic acid, pamoic acid, and 8-chlorotheophylline with various basic moieties were readily and effectively resolved into their ionic components using almost identical RP-HPLC conditions.

Chromatography, High Pressure Liquid↗