Radioreceptor and High‐Performance Liquid Chromatographic Assays for the Calcium Channel Antagonist Nitrendipine in Serum

Janis, R.A.; Krol, G.J.; Noe, Anson; Pan, Mary

doi:10.1002/j.1552-4604.1983.tb02734.x

Cited by 40 publications

(5 citation statements)

References 14 publications

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“…The specificity of the antibodies was then determined by comparing the concentration required for half-maximal inhibition of [3H]nitrendipine-antibody binding. As shown in Table 1, A comparison of the specificity of the anti-dihydropyridine antibodies and the membrane receptor has also been made using metabolites of nitrendipine (31), which are not active in inhibiting Ca2+-channel activity or [3Hlnitrendipine binding to the membrane receptor (7,31). As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers.

Campbell¹,

Sharp²,

Strom³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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Antibodies with affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers have been produced in rabbits by immunization with dihydropyridine-protein conjugates. Drugs that block these voltage-dependent Ca2' channels are used for the treatment of various cardiovascular disorders and are referred to as Ca2+-channel blockers (4-8).Nifedipine, nitrendipine, nisoldipine, and related 1,4-dihydropyridines are the most potent class of Ca2+-channel blockers, and radiolabeled dihydropyridines have been shown to bind with high affinity to membranes isolated from cardiac, skeletal, and smooth muscle (9-13). To better understand the mechanism of action of the dihydropyridine Ca2+-channel blockers, investigators have undertaken the identification of the membrane receptor for these drugs in cardiac and skeletal muscle (14-16) and the isolation and purification of the membrane receptor from enriched sources (i.e., transverse tubular membrane of skeletal muscle) (17)(18)(19). Considerable advances have been made in recent years in the structural and functional characterization of membrane receptors and ion channels by using immunological probes (20)(21)(22)(23)(24)(25)(26). Antibodies have been raised against membrane receptors or ion channels directly by immunization with purified membrane proteins or indirectly by immunization with anti-ligand antibodies to produce anti-idiotypic antibodies. Anti-idiotypic antibodies have been very useful in studying receptor structure and function, because these antibodies bind to the ligand binding site on the receptor and in some cases can modify receptor function (21). Anti-ligand antibodies (20,21,23,(26)(27)(28)(29) have been used to study structureactivity relationships between the ligand and antibody and as specific molecules that can compete with the receptor for the ligand.We report here the production of high-affinity antibodies specific for the 1,4-dihydropyridine Ca2+-channel blockers by using either a bovine serum albumin-dihydropyridine conjugate or a keyhole limpet hemocyanin-dihydropyridine conjugate. The dihydropyridine-protein conjugates were prepared by using an affinity analog of nifedipine-1,4-dihydro -2,6 -dimethyl -4 -(2 -isothiocyanatophenyl) -3,5-pyridinedicarboxylic acid dimethyl ester (nifedipine-isothiocyanate)-that can covalently react with free amino groups in both proteins to form a covalent dihydropyridine-protein conjugate. Anti-dihydropyridine antibodies have been found to bind [3H]nitrendipine with high affinity and specificity.The dihydropyridine binding properties of the antidihydropyridine antibodies suggest that the antibodies resemble the membrane receptor for the 1,4-dihydropyridine Ca2+-channel blockers with respect to affinity and specificity of 1,4-dihydropyridine binding. MATERIALS AND METHODSPreparation of Dihydropyridine-Protein Conjugates.Nifedipine-isothiocyanate was used to couple nifedipine covalently to various carrier proteins (i.e., bovine serum albumin, ovalbumin, and keyhole limpet hemocyanin). The carrier protei...

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Section: Discussionmentioning

confidence: 99%

“…Fig. 3 shows the results of a typical competitive radioimmunoassay used for the determination of the affinity The specificity of the anti-dihydropyridine antibodies has also been examined by testing the ability of inactivated forms of the Ca2"-channel blockers (31,32) …”

Section: Methodsmentioning

confidence: 99%

High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers.

Campbell¹,

Sharp²,

Strom³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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“…Plasma samples were analyzed for nitrendipine concentration using high performance liquid chromatography (HPLC) with UV detection at a wavelength of 238 nm (Janis et al, 1983). The internal standard nimodipine (40 ng, in 20 mL methanol) was mixed with plasma sample (1 mL) and 0.4 mL 1.0 N NaOH solution.…”

Section: Analysis Of Nitrendipine In Plasmamentioning

confidence: 99%

In Vivo Evaluation of Two Novel Controlled-Release Nitrendipine Formulations

Yang

Cui

You

et al. 2005

Drug Development and Industrial Pharmacy

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The objective of this work is to assess two novel controlled-release nitrendipine formulations, i.e., sustained-release nitrendipine microspheres having solid dispersion structure and a novel pH-dependent gradient-release delivery system for nitrendipine in healthy male volunteers, which were prepared by current authors. Domestic commercial nitrendipine tablets and Baypress nitrendipine tablets were employed as reference formulations. In a randomized, single-dose, fasting-state, crossover study design with a 1-week washout period, each subject received a 40-mg nitrendipine formulation. Plasma samples were collected over a 25-hour period after oral administration and were analyzed by a validated method using high performance liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were determined using a noncompartmental analysis. The results provided evidence that the time to maximum plasma concentration of two novel controlled-release nitrendipine formulations were statistically significant prolonged in comparison with that of Baypress nitrendipine tablets. The relative bioavailabilities of test formulations were intensively improved compared with the domestic nitrendipine tablets, while the ratio is in a range of 80-120% in comparison with Baypress nitrendipine tablets. It is concluded that the two types of controlled-release systems are feasible for improving the dissolution rate of nitrendipine and obtaining a long-acting in vivo as well.

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“…1) is a potent vasodilator with antihypertensive activity (Santiago and Lopez, 1990), whose effects are related to calcium channel inhibiting properties. Many analytical methods for estimation of nitrendipine in biological samples have been reported (Janis et al, 1983;Beck et al, 1985;Fischer et al, 1986;Soons and Breimer, 1988;Heinig and Bucheli, 2002). However, there are some problems with these reported methods.…”

Section: Introductionmentioning

confidence: 96%

Development and validation of a reversed‐phase HPLC method for determination of nitrendipine in rat plasma: application to pharmacokinetic studies

Venishetty

Durairaj

Sistla

et al. 2007

Biomedical Chromatography

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A simple and sensitive method for the determination of nitrendipine in rat plasma was developed using high-performance liquid chromatography (HPLC). The procedure involves extraction of nitrendipine in dichloromethane/sodium hydroxide, followed by reversed phase HPLC using a Waters, Spherisorb ODS2 (250 x 4.6 mm, 5 microm) column and UV detection at 238 nm. The retention times of nitrendipine and internal standard (felodipine) were 5.0 min and 7.5 min, respectively. The calibration curves were linear over the range of 5 ng/mL (lower limit of quantification, LOQ) to 200 ng/mL for nitrendipine. The intra- and inter-day coefficients of variation for all criteria of validation were less than 15% over the linearity range. The sensitivity and precision of the method were within the accepted limits (< 15%) throughout the validation period. The present method was also successfully applied for the study of plasma pharmacokinetics of nitrendipine loaded solid lipid nanoparticles (SLN) in rats.

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Radioreceptor and High‐Performance Liquid Chromatographic Assays for the Calcium Channel Antagonist Nitrendipine in Serum

Cited by 40 publications

References 14 publications

High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers.

High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers.

In Vivo Evaluation of Two Novel Controlled-Release Nitrendipine Formulations

Development and validation of a reversed‐phase HPLC method for determination of nitrendipine in rat plasma: application to pharmacokinetic studies

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