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*****AMERICAN JOURNAL OF GASTROENTEROLOGY*****

Nadir A Agrawal S King PD Marshall JB

Acute hepatitis associated with the use of a Chinese herbal product, ma-

huang

[see comments]

In: Am J Gastroenterol (1996 Jul) 91(7):1436-8

ISSN: 0002-9270



Herbal medicines are widely perceived by the public as being healthful

and

innocuous. A number of herbal medicines have now been linked with

hepatotoxicity. We report a case of acute hepatitis associated with the

use of

ma-huang, a herbal product derived from plants of the Ephedra species,

which is

advertised as being useful for causing weight loss and enhancing energy

levels.

Given the lack of reports in the literature of hepatotoxicity with ma-

huang and

ephedrine, we speculate that the ma-huang product our patient took

contained

some other ingredient or contaminant or was misidentified. Our report and

others

in the literature, which we review, indicate that the clinician should

consider

herbal medicines as a possible cause of unexplained liver injury.



Registry Numbers:

299-42-3 (Ephedrine)



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*****EMBO JOURNAL*****

Malek O Lattig K Hiesel R Brennicke A Knoop V

RNA editing in bryophytes and a molecular phylogeny of land plants.

In: EMBO J (1996 Mar 15) 15(6):1403-11

ISSN: 0261-4189



RNA editing has been observed to date in all groups of vascular plants,

but not

in bryophytes. Its occurrence was therefore assumed to correlate with the

evolution of tracheophytes. To gain more insight into both the phylogeny

of

early land plants and the evolution of mitochondrial RNA editing we have

investigated a number of vascular and non-vascular plant species.

Contrary to

the belief that editing is absent from bryophytes, here we report

mitochondrial

RNA editing in cox3 mRNA of the liverwort Pellia epiphylla, the mosses

Tetraphis

pellucida and Ceratodon purpureus and the hornwort Anthroceros crispulus.

RNA

editing in plants consequently predates the evolution of tracheophytes.

Editing

is also found in the eusporangiate ferns Ophioglossum petiolatum and

Angiopteris

palmiformis, the whisk fern Tmesipteris elongata and the gnetopsid

Ephedra

gerardiana, but was not detected in Gnetum gnemon.cox3 mRNA of the

lycopsid

Isoetes lacustris shows the highest frequency of RNA editing ever

observed in a

plant, with 39% of all cytidine residues converted to uridines. The

frequency of

RNA editing correlates with the genomic GC content rather than with the

phylogenetic position of a species. Phylogenetic trees derived from the

slowly

evolving mitochondrial sequences find external support from the

assessments of

classical systematics.



Registry Numbers:

EC 1.9.3.1 (Cytochrome-c Oxidase)



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*****ADVANCES IN BIOCHEMICAL ENGINEERING/BIOTECHNOLOGY*****

Rogers PL Shin HS Wang B

Biotransformation for L-ephedrine production.

In: Adv Biochem Eng Biotechnol (1997) 56:33-59

ISSN: 0724-6145



L-ephedrine is widely used in pharmaceutical preparations as a

decongestant and

anti-asthmatic compound. One of the key intermediates in its production

is

L-phenylacetylcarbinol (L-PAC) which can be obtained either from plants

(Ephedra

sp.), chemical synthesis involving resolution of a racemic mixture, or by

biotransformation of benzaldehyde using various yeasts. In the present

review,

recent significant improvements in the microbial biotransformation are

assessed

for both fed-batch and continuous processes using free and immobilised

yeasts.

From previous fed-batch culture data, maximal levels of L-PAC of 10-12

gl-1 were

reported with yields of 55-60% theoretical based on benzaldehyde.

However,

recently concentrations of more than 22 gl-1 have been obtained using a

wild-type strain of Candida utilis. This has been achieved through

optimal

control of yeast metabolism (via microprocessor control of the

respiratory

quotient, RQ) in order to enhance substrate pyruvate production and

induce

pyruvate decarboxylase (PDC) activity. Processes involving purified PDC

have

also been evaluated and it has been demonstrated that L-PAC levels up to

28 gl-1

can be obtained with yields of 90-95% theoretical based on the

benzaldehyde

added. In the review the advantages and disadvantages of the various

strategies

for the microbial and enzymatic production of L-PAC are compared. In view

of the

increasing interest in microbial biotransformations, L- PAC production

provides

an interesting example of enhancement through on-line control of a

process

involving both toxic substrate (benzaldehyde) and end-product (L-PAC,

benzyl

alcohol) inhibition.



Registry Numbers:

EC 4.1.1.1 (Pyruvate Decarboxylase)

100-52-7 (benzaldehyde)

299-42-3 (Ephedrine)

67-64-1 (Acetone)

90-63-1 (1-hydroxy-1-phenyl-2-propanone)



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*****AMERICAN JOURNAL OF CHINESE MEDICINE*****

Mahdihassan S Mehdi FS

Soma of the Rigveda and an attempt to identify it.

In: Am J Chin Med (1989) 17(1-2):1-8

ISSN: 0192-415X



Ephedra juice is used as the drink of longevity given even to the new

born. This

is an Aryan custom mentioned in Rigveda and followed even by the Romans.

To

trace the history of this custom would lead to identifying Soma =

Ephedra. The

original species of Ephedra or Soma proper would be Ephedra sinica, the

Chinese

plant. It is the one species with yellow stalks. This has been

illustrated so

that it confirms Rigveda speaking of Soma as "golden yellow." The name

Soma is

also a loan word from Chinese meaning "fire-yellow fibers of hemp." The

plant

Soma is described as "thousand boughs" and photographic evidence has been

offered in support. Each stalk is rod- like resembling an arrow as

Rigveda

speaks of it. An illustration has been offered to show the plant with

stalks

which are straight and rod- like, comparable with an arrow.

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*****AMERICAN JOURNAL OF NEPHROLOGY*****

Chan EL Ahmed TM Wang M Chan JC

History of medicine and nephrology in Asia.

In: Am J Nephrol (1994) 14(4-6):295-301

ISSN: 0250-8095



The beginning of Chinese medicine has been attributed to 3 mythical

emperors who

gathered herbs for medicines. During the 2nd century BC, Han dynasty

physicians

developed cranial trephining and sedation with wine and herbs for

anesthesia.

Chiang Chung-Ching (142-212 AD) used the appearance of rashes in

diagnosis,

treated infections with anthelmintics and asthma with ephedra, described

the

symptoms of diabetes mellitus and expanded medical ethics. The

specialties of

obstetrics, pediatrics, ophthalmology and dentistry were described in the

records of the Han and Tang dynasties, and methods of setting fractures

and

treating trauma were comparable with those of Roman military doctors.

Shen Tua

(1031-1095 AD) compiled a pharmacopeia and studied acupuncture and the

pulses.

Forensic medicine was developed during the 10th century by Sung Tse, who

also

advocated hand washing with sulfur and vinegar to avoid infection during

autopsies. The Daoist physicians used androgens and estrogens to treat

hypogonadism with therapeutic preparations of placentas. They also had an

advanced knowledge of alchemy, claiming to achieve 'immortality' by their

preservation techniques. Qualifying examinations for physicians were

conducted

by the Chinese state as early as the 1st century AD, and later

incorporated

philosophy and art to conform with the Confucian ideal. Throughout these

eras,

Chinese medicine profited from contact with western Asia. In ancient

Chinese

medicine, the excretory function of the kidney was attributed to the

bladder.

'Kidney weakness', which refers to somatized depression, was treated by

acupuncture along the 'kidney channel'. Pulse examination was also used

to give

a measure of the imbalance of renal Yin and Yang.(ABSTRACT TRUNCATED AT

250

WORDS)



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*****ARCHIV FUR EXPERIMENTELLE VETERINARMEDIZIN*****

Shabana MM Mirhom YW Genenah AA Aboutabl EA Amer HA

Study into wild Egyptian plants of potential medicinal activity. Ninth

communication: hypoglycaemic activity of some selected plants in normal

fasting

and alloxanised rats.

In: Arch Exp Veterinarmed (1990) 44(3):389-94

ISSN: 0003-9055



31 desert plants belonging to 17 families were collected from different

Egyptian

localities. 21 plants extracts were orally given to normal rats, and 15

were

tested on fasted and to alloxanised rats. The results were compared with

a

standard oral hypoglycaemic drug (Daonil, Hoechst) used as a positive

control.

The following findings were obtained: 8 plants exhibited persistent

hypoglycaemic effects, Lycium shawii, Salvia (S.) aegyptiaca, Pergularia

tomentosa, Convolvulus (C.) althaeoides, Haloxylon salicornicum, Ephedra

alata,

Scrophularia deserti, and Crotalaria aegyptiaca. Transient hypoglycaemic

effects

appeared only 1 hour after administration in response to 4 plants, Silena

succulenta, Lygos raetam, C. lanatus, and Pulicaria incisa. In the cases

of

Ochradenus baccatus and Zygophyllum album, slow hypoglycaemic activity

was

produced and appeared 3 hours after administration. 5 plants showed

hypoglycaemic effects viz, Thymus capitatus, Launaea nudicaulis, Conyza

dioscorides, Nitraria retusa, and Limonium tubiflorum. Among the 15 plant

extracts tested on alloxanised diabetic rats only 4 showed hypoglycaemic

effects

more potent than those of the administered dose of Daonil. These were

Matthiola

livida, S. aegyptiaca, Astragalus species, and Arthrocnemum glaucum. The

hypoglycaemic effect of S. aegyptiaca in fasting rats has been confirmed

also in

alloxanised diabetic animals. This emphasises the importance of

conducting both

experiments in order to obtain a reliable conclusion.



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*****BIOCHIMICA ET BIOPHYSICA ACTA*****

Melekhovets YuF Troitsky AV

Comparative analysis of 5.8 S rRNA from Ephedra kokanica Regl.

(Gymnospermae)

and other plant species.

In: Biochim Biophys Acta (1990 Apr 6) 1048(2-3):294-6

ISSN: 0006-3002



5.8 S rRNA from the gymnosperm Ephedra kokanica Regl. (EMBL Data Library

accession No. X15676) has been sequenced. It is 161 nucleotides long and

contains three 2'-O-methylated residues--two adenosines and one

guanosine. No

pseudouridine have been detected. E. kokanica 5.8 S rRNA, as those from

other

plant species, can form a secondary structure with paired 5'- and 3'-

terminal

regions. 5.8 S rRNAs of seed plants differ from the moss Mnium reguicum

5.8 S

rRNA in that they have longer variable 'GC-rich' hairpins with insertions

in the

loop region. 5.8 S rRNA of E. kokanica reveals 69 and 82% of homology

with that

of moss and five angiosperm species, respectively. The

posttranscriptional

modification pattern of plant 5.8 S rRNAs is not strictly conservative.



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*****CANCER LETTERS*****

Tricker AR Wacker CD Preussmann R

Nitrosation products from the plant Ephedra altissima and their potential

endogenous formation.

In: Cancer Lett (1987 May) 35(2):199-206

ISSN: 0304-3835



The plant species Ephedra is commonly used in both folk medicine and for

the

preparation of health teas. Nitrosation of a tea made from Ephedra

altissima

yielded N-nitrosoephedrine (NEP), N- nitrosopseudoephedrine (NPEP),

N-nitrosoproline (NPRO), N- nitrosomethylbenzylamine (NMBA), trace

quantities of

2 unidentified non-volatile nitrosamines and the new nitroso compound

2-(N-nitroso-N- methylamino)propiophenone (NMAP). Incubation of a tea

extract at

37 degrees C and pH 2.0 under conditions simulating the normal fasting

stomach

with a constant nitrite concentration (25 microM) for 1 h produced NEP,

NPEP,

NMAP and NPRO. The synthesis and preliminary results for the mutagenic

effect of

NMAP on the reversion of Salmonella typhimurium strains TA100 and TA1535

in the

Ames test are reported.



Registry Numbers:

110505-04-9 (2-(N-nitroso-N-methylamino)propiophenone)

17608-59-2 (N-nitrosoephedrine)

62-75-9 (Dimethylnitrosamine)

7519-36-0 (nitrosoproline)

937-40-6 (nitrosobenzylmethylamine)



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Alwan SM Al-Hindawi MK Abdul-Rahman SK Al-Sarraj S

Production of nitrosamines from ephedrine, pseudoephedrine and extracts

of

Ephedra foliata under physiological conditions.

In: Cancer Lett (1986 May) 31(2):221-6

ISSN: 0304-3835



N-Nitrosoephedrine (NEP) and N-nitrosopseudoephedrine (NPEP) were

synthesised at

5 degrees C using different concentrations of various acids. The reaction

with

acetic acid gave the highest yield (85%) of N-nitrosamine. Ephedrine and

pseudoephedrine were reacted with nitrite under physiological conditions

(37

degrees C, pH 1-3) to form NEP and NPEP. The yield of NEP, which is a

known

carcinogen, and NPEP were the highest (18.5%) at pH 2. Aqueous and

alcoholic

extracts of Ephedra foliata (100 g dry wt), nitrosated under

physiological

conditions, produced 0.77 mg and 8.3 mg, respectively, as total

nitrosamines.

This indicated the potential of the nitrosamine formation from the plant

extracts specified.



Registry Numbers:

299-42-3 (Ephedrine)

7632-00-0 (Sodium Nitrite)



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*****CHUNG-KUO CHUNG HSI I CHIEH HO TSA CHIH*****

Wang GZ Hikokichi O

[Experimental study in treating chronic renal failure with dry extract

and

tannins of herba ephedra]

In: Chung Kuo Chung Hsi I Chieh Ho Tsa Chih (1994 Aug) 14(8):485-8

ISSN: 1003-5370 (Published in Chinese)



The effects of dry extract and tannin of Herba Ephedra on adenine-

induced

chronic renal failure in rats and their mechanisms of action have been

studied.

Dry extract of Herba Ephedra in dose of 10 mg, 20 mg and 30 mg/d with

adenine

(for 24 days) were administered to rats. After inducing renal failure (34

days),

it reduced toxins in blood significantly. The action of 30 mg-dose was

highly

significant, BUN decreased by 37%, creatinine (Cr) 35%, methylguanidine

(MG)

76%, guanidinosuccinic acid 83%, blood phosphate 39%, while blood calcium

raised

for 28%. But in 25mg and 45mg-dose, MG in urine decreased by 49%-65%. The

mechanisms of action might be including (1) Inhibiting the production of

Cr; (2)

Inhibiting the production of hydroxyl free radical, blocking the

conversion of

Cr into creatol, thereby reducing, the production of MG from creatol. In

conclusion, dry extract of Herba ephedra could improve renal function in

adenine- induced chronic renal failure in rats, correct Ca and P

disorder, and

especially inhibit the production of MG. Fraction 2 and fraction 3 of

Ephedra

tannin had no effect on this renal failure model.



Registry Numbers:

471-29-4 (Methylguanidine)

73-24-5 (Adenine)



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**CHUNG-KUO CHUNG YAO TSA CHIH CHINA JOURNAL OF CHINESE MATERIA MEDICA*

Zeng Q Liu C Lou G Zheng L Jiang H

[Volatile oil in Ephedra sinica Stapf. and its processed products by GC-

MS]

In: Chung Kuo Chung Yao Tsa Chih (1992 Feb) 17(2):83-7, 126

ISSN: 1001-5302 (Published in Chinese)



This paper deals with the changes in contents and chemical composition in

the

volatile oil of Ephedra sinica before and after processing. The results

indicate

that after processing, the more the substances of low boiling point, the

higher

their contents and vice versa. The changes are particularly obvious in

yellow-fried Ephedra sinica.



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*****CLINICAL AND EXPERIMENTAL IMMUNOLOGY*****

Ling M Piddlesden SJ Morgan BP

A component of the medicinal herb ephedra blocks activation in the

classical and

alternative pathways of complement.

In: Clin Exp Immunol (1995 Dec) 102(3):582-8

ISSN: 0009-9104



Extracts of the herb Ephedra sinica have long been used in traditional

Chinese

medicine for the treatment of, among other conditions, acute nephritis.

In

preliminary studies it was shown that extracts of ephedra caused

inhibition of

complement in vitro. We thus set out to isolate the active component(s)

of this

herb, to examine the complement-inhibiting capacity in sera from

different

species, and to characterize the mechanism(s) by which it inhibits

complement.

Aqueous extraction of the herb followed by fractionation using thin layer

chromatography (TLC) demonstrated that complement-inhibiting activity

resided

within a single band, hereafter termed the complement-inhibiting

component

(CIC), which represents an as yet uncharacterized polyanionic

carbohydrate

molecule. TLC-purified CIC inhibited the classical complement pathway in

all

species tested (human, pig, guinea pig, rat and rabbit). Using

erythrocyte

intermediates and sera specifically depleted of individual components it

was

apparent that CIC inhibited C2. This finding was confirmed using purified

human

C2, CIC causing a dose-dependent loss of C2 haemolytic activity. At much

higher

doses, CIC also showed some inhibiting effect in the terminal pathway,

and this

was shown to be due to inhibition of C9. In the alternative pathway CIC

also

showed inhibitory activity, although its site of action in this pathway

remains

unresolved. In Chinese medicine the herb is taken orally, though no

studies of

complement levels in patients taking the herb have been reported.

Preliminary

data indicate that oral administration in rats causes a partial

inhibition of

serum complement activity. Given the current enthusiasm for complement

inhibition as a therapy for inflammatory diseases, this non-toxic,

naturally

occurring agent might be of therapeutic value.



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*****JOURNAL OF AOAC INTERNATIONAL*****

Betz JM Gay ML Mossoba MM Adams S Portz BS

Chiral gas chromatographic determination of ephedrine-type alkaloids in

dietary

supplements containing Ma Huang.

In: J AOAC Int (1997 Mar-Apr) 80(2):303-15

ISSN: 1060-3271



Ma Huang is a traditional Chinese medicine derived from the aerial parts

of

several Ephedra species (Ephedraceae). These plants produce (-)-

ephedrine,

(+)-pseudoephedrine, (-)-norephedrine, (+)- norpseudoephedrine,

(-)-N-methylephedrine, and (+)-N- methylpseudoephedrine. Racemic and

(-)-ephedrine, (+)- pseudoephedrine, and (+/-)-norephedrine

(phenylpropanolamine) are used clinically in the United States and are

largely

synthetic in origin. Current interest in Ma Huang is spurred by reports

describing a "thermogenic" (calorie burning) effect provided by mixtures

of

ephedrine, caffeine, and aspirin. Products providing the key thermogenic

compounds from natural sources are available as dietary supplements in

retail

outlets. Reports of potentially unsafe levels of the alkaloids, as well

as

possible fortification of Ma Huang- containing products with synthetic

Ephedra

alkaloids, prompted the development of a chiral gas chromatographic (GC)

method

that allows determination of alkaloid patterns and identification of

isomerically impure synthetic alkaloids. Nine products were analyzed on a

gamma-

cyclodextrin capillary GC column. Identity of the alkaloids was verified

by

GC/mass spectrometry (MS) and GC/matrix isolation/Fourier transform

infrared

spectroscopy. No synthetic isomers were found in the dietary supplements

analyzed. Three products contained only one of the ephedrine-type

alkaloids. One

product that listed Ma Huang as an ingredient contained no detectable

ephedrine-type alkaloid. In products containing measurable quantities of

these

compounds, total alkaloid levels ranged from 0.3 to 56 mg/g.



Registry Numbers:

299-42-3 (Ephedrine)



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Hanna GM

Determination of ephedrine, pseudoephedrine, and norephedrine in mixtures

(bulk

and dosage forms) by proton nuclear magnetic resonance spectroscopy.

In: J AOAC Int (1995 Jul-Aug) 78(4):946-54

ISSN: 1060-3271



A simple, specific, and accurate 1H nuclear magnetic resonance (NMR)

spectroscopic method has been developed for quantitative determination of

the

Ephedra alkaloids (-)-ephedrine, (+)- pseudoephedrine, and (+/-)-

norephedrine,

either singly or in mixtures with each other. Determination of individual

alkaloids was carried out in D2O solution, with acetamide as internal

standard.

Although calculations were based on integrals for the C-CH3 protons,

those for

the N-CH3 and -CH-O- protons may also be useful, depending on the

compound.

Determination of diastereomeric cross-contamination of ephedrine and

pseudoephedrine--or of the concentrations of these alkaloids in the

presence or

absence of (+/-)-norephedrine--was feasible by using the integrals for

the

-CH-O- protons after addition of a trace of DCl. Mean recoveries for

ephedrine

and pseudoephedrine from their respective synthetic mixtures with the

internal

standard (acet- amide) were > or = 99.9 +/- 0.6% (n = 10) and 99.6 +/-

0.8% (n =

10) of the amount added. Recovery for pseudoephedrine from diastereomeric

mixtures with ephedrine was > 99.4 +/- 0.7% (n = 10) of the amount added,

with

as little as 1.92% still being measurable. Mean recovery of (+/-)-

norephedrine

from mixtures with ephedrine and pseudoephedrine was > 99.7 +/- 2.5% (n =

4) of

the amount added, with about 1% still being measurable. Application of

the

proposed NMR spectroscopic method to commercial dosage forms, including

ephedrine sulfate injections and pseudoephedrine hydrochloride tablets,

yielded

assay results ranging from 97.8 to 100.2% (mean, 99.2%) and from 98.7 to

100.5%

(mean, 99.7%) of declared, respectively.



Registry Numbers:

14838-15-4 (Phenylpropanolamine)

299-42-3 (Ephedrine)



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*****JOURNAL OF CHROMATOGRAPHY. B, BIOMEDICAL APPLICATIONS*****

Flurer CL Lin LA Satzger RD Wolnik KA

Determination of ephedrine compounds in nutritional supplements by

cyclodextrin-modified capillary electrophoresis.

In: J Chromatogr B Biomed Appl (1995 Jul 7) 669(1):133-9

ISSN: 0378-4347



Capillary electrophoresis was utilized for the separation,

identification, and

quantitation of ten stereoisomers in the ephedrine family. Chiral

discrimination

was accomplished through the use of hydroxypropyl-beta-cyclodextrin, and

separation was enhanced at pH 2 in the presence of tetramethylammonium

chloride

and sodium dodecyl sulfate. Calibration plots of the ephedrines were

linear over

the range 4-100 micrograms/ml. This method was used in the analysis of

nutritional supplements that contain Ma Huang, a Chinese herbal

preparation that

is made from plants in the genus Ephedra.



Registry Numbers:

299-42-3 (Ephedrine)



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*****JOURNAL OF ETHNOPHARMACOLOGY*****

Lietava J

Medicinal plants in a Middle Paleolithic grave Shanidar IV?

In: J Ethnopharmacol (1992 Jan) 35(3):263-6

ISSN: 0378-8741



This paper deals with phytopharmacological evaluation of the therapeutic

potential of the plants found in the Neanderthal grave of a Shanidar IV

individual (Iraq), where the palynological analysis of some other authors

discovered the following flowers: Achillea-type, Centaurea solstitialis,

Senecio-type, Muscari-type, Ephedra altissima, Althea-type. The purpose

of our

theoretical analysis was to evaluate the objective healing activity of

the

flowers. The result of the research revealed that Shanidar IV flowers

possess

considerable therapeutic effects with marked medical activity, which

could be an

intentional reason for the selection of the flowers in Middle Paleolithic

Shanidar Neanderthals.



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Kalix P

The pharmacology of psychoactive alkaloids from ephedra and catha.

In: J Ethnopharmacol (1991 Apr) 32(1-3):201-8

ISSN: 0378-8741



Ever since the introduction of the alkaloid ephedrine as an anti-

asthmatic, the

CNS stimulatory effects of this sympathomimetic have been a problem in

therapy.

Indeed, the use of ephedrine is not only limited by its cardiovascular

effects,

but also by the occurrence of insomnia, restlessness and anxiety.

Exceptionally,

ephedrine may even induce toxic psychosis, and the possibility of this

side

effect has recently received renewed attention. Besides ephedrine, the

ephedra

plant contains some norpseudoephedrine. This substance is also called

cathine,

because it is a major alkaloid of Catha edulis or khat, a plant that is

widely

used as a stimulant in certain countries of East Africa and of the Arab

Peninsula. The effects of khat have been explained formerly by those of

cathine;

some time ago, however, the labile alkaloid cathinone was discovered in

khat.

This substance is the keto-analog of cathine; it is therefore more

lipophilic

and penetrates easily to its sites of action in the central nervous

system.

Indeed, cathinone has been found to be a highly potent CNS stimulant and

it is

now known to be the main psychoactive constituent of khat; the results of

various in vitro and in vivo studies indicate that cathinone must be

considered

a natural amphetamine. In confirmation of this view, it has recently been

demonstrated that cathinone has in humans marked euphorigenic and

psychostimulant effects. As the case may be, these findings may lead,

together

with epidemiological data, to a reconsideration of the use of khat as a

stimulant and social drug.



Registry Numbers:

299-42-3 (Ephedrine)



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



*****JOURNAL OF MOLECULAR EVOLUTION*****

Troitsky AV Melekhovets YuF Rakhimova GM Bobrova VK Valiejo-Roman KM

Antonov AS

Angiosperm origin and early stages of seed plant evolution deduced from

rRNA

sequence comparisons.

In: J Mol Evol (1991 Mar) 32(3):253-61

ISSN: 0022-2844



Complete or partial nucleotide sequences of five different rRNA species,

coded

by nuclear (18S, 5.8S, and 5S) or chloroplast genomes (5S, 4.5S) from a

number

of seed plants were determined. Based on the sequence data, the

phylogenetic

dendrograms were built by two methods, maximum parsimony and

compatibility. The

topologies of the trees for different rRNA species are not fully

congruent, but

they share some common features. It may be concluded that both

gymnosperms and

angiosperms are monophyletic groups. The data obtained suggest that the

divergence of all the main groups of extant gymnosperms occurred after

the

branching off of the angiosperm lineage. As the time of divergence of at

least

some of these gymnosperm taxa is traceable back to the early

Carboniferous, it

may be concluded that the genealogical splitting of gymnosperm and

angiosperm

lineages occurred before this event, at least 360 million years ago,

i.e., much

earlier than the first angiosperm fossils were dated. Ancestral forms of

angiosperms ought to be searched for among Progymnospermopsida.

Genealogical

relationships among gymnosperm taxa cannot be deduced unambiguously on

the basis

of rRNA data. The only inference may be that the taxon Gnetopsida is an

artificial one, and Gnetum and Ephedra belong to quite different lineages

of

gymnosperms. As to the phylogenetic position of the two Angiospermae

classes,

extant monocotyledons seem to be a paraphyletic group located near the

root of

the angiosperm branch; it emerged at the earliest stages of angiosperm

evolution. We may conclude that either monocotyledonous characters arose

independently more than once in different groups of ancient Magnoliales

or that

monocotyledonous forms rather than dicotyledonous Magnoliales were the

earliest

angiosperms. Judging by the rRNA trees, Magnoliales are the most ancient

group

among dicotyledons. The most ancient lineage among monocotyledons leads

to

modern Liliaceae.



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



Kolukisaoglu HU Marx S Wiegmann C Hanelt S Schneider-Poetsch HA

Divergence of the phytochrome gene family predates angiosperm evolution

and

suggests that Selaginella and Equisetum arose prior to Psilotum.

In: J Mol Evol (1995 Sep) 41(3):329-37

ISSN: 0022-2844



Thirty-two partial phytochrome sequences from algae, mosses, ferns,

gymnosperms,

and angiosperms (11 of them newly released ones from our laboratory) were

analyzed by distance and character-state approaches (PHYLIP, TREECON,

PAUP). In

addition, 12 full-length sequences were analyzed. Despite low bootstrap

values

at individual internal nodes, the inferred trees (neighbor-joining,

Fitch,

maximum parsimony) generally showed similar branching orders consistent

with

other molecular data. Lower plants formed two distinct groups. One basal

group

consisted of Selaginella, Equisetum, and mosses; the other consisted of a

monophyletic cluster of frond-bearing pteridophytes. Psilotum was a

member of

the latter group and hence perhaps was not, as sometimes suggested, a

close

relative of the first vascular plants. The results further suggest that

phytochrome gene duplication giving rise to a- and b- and later to c-

types may

have taken place within seedfern genomes. Distance matrices dated the

separation

of mono- and dicotyledons back to about 260 million years before the

present

(Myr B.P.) and the separation of Metasequoia and Picea to a fossil

record-compatible value of 230 Myr B.P. The Ephedra sequence clustered

with the

c- or a-type and Metasequoia and Picea sequences clustered with the b-

type

lineage. The "paleoherb" Nymphaea branched off from the c-type lineage

prior to

the divergence of mono- and dicotyledons on the a- and b-type branches.

Sequences of Piper (another "paleoherb") created problems in that they

branched

off from different phytochrome lineages at nodes contradicting distance

from the

inferred trees' origin.



Registry Numbers:

11121-56-5 (Phytochrome)



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



*****JOURNAL OF PHARMACOBIO-DYNAMICS*****

Harada M Nishimura M

Contribution of alkaloid fraction to pressor and hyperglycemic effect of

crude

Ephedra extract in dogs.

In: J Pharmacobiodyn (1981 Sep) 4(9):691-9



In anesthetized dogs, pressor and hyperglycemic effects of Ephedra

aqueous

extract as well as its alkaloid fraction and adsorption of alkaloid from

the

digestive tract were studied in order to investigate how closely effects

of the

alkaloid fraction relate to those of the Ephedra extract itself. Blood

pressure,

heart rate, and blood glucose concentration were increased by

intraduodenal

administration of the extract and the alkaloid fraction on the bases of

the same

alkaloid content (20 mg/Kg). In respect to the pressor and hyperglycemic

effects, changes in time course of the effects produced by these two drug

preparations were similar and in either of the two physiological

parameters the

maximal value given by the extract was about a half that given by the

alkaloid

fraction. A maximal level of blood pressure and blood glucose

concentration was

reached 10-15 min after the administration of the two drug preparations,

while

the amount of alkaloid absorbed in the portal vein until this time was

about 2-3

times as much under administration of the alkaloid fraction as under

administration of the extract. Absorption of alkaloid in the extract

occurred

slowly and lasted longer compared with that of the alkaloid fraction

itself. On

the contrary, the alkaloid-free extract administered intraduodenally

showed no

virtual effects on blood pressure and blood glucose concentration except

producing tachycardia. It seems that the effect of Ephedra extract on

blood

pressure and blood glucose concentration was mostly qualitatively and

quantitatively represented by that of alkaloid contained and that effect

of the

extract mainly depended on that of alkaloid absorbed early after its

application.



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



*****MOLECULAR PHYLOGENETICS AND EVOLUTION*****

Boivin R Richard M Beauseigle D Bousquet J Bellemare G

Phylogenetic inferences from chloroplast chlB gene sequences of

Nephrolepis

exaltata (Filicopsida), Ephedra altissima (Gnetopsida), and diverse land

plants.

In: Mol Phylogenet Evol (1996 Aug) 6(1):19-29

ISSN: 1055-7903



The chloroplast chlB gene, involved in light-independent

protochlorophyllide

reduction, has been reported present in algae, in one bryophyte and some

gymnosperms, but absent from various angiosperms. In this study, the

complete or

nearly complete chlB gene sequences from the fern Nephrolepis exaltata

and the

seed plant Ephedra altissima were determined. Comparison of five

available land

plant chlB sequences with a similar set of rbcL sequences, encoding the

large

subunit of ribulose 1,5-bisphosphate carboxylase, showed that the chlB

rate of

nonsynonymous substitution was about fourfold higher than for rbcL, while

the

chlB phylogeny resulted in a better resolution of the clades surveyed.

The

presence of chlB in other lineages of land plants was determined by

amplification and sequencing of a chlB internal fragment, which was

recovered

from all the nonangiosperm taxa surveyed except Psilotum and Gnetum. The

phylogenies derived from 23 land plant chlB sequences were largely

congruent

with the relationships inferred from other analyses. Neighbor-joining

analysis

supported the view that bryophytes are paraphyletic, with mosses as

sister group

to vascular plants. Within lycopodiophytes, Selaginella clustered with

Lycopodium, but Isoetes was located basally to the other land plants. The

various ferns surveyed were found to form a coherent group which derived

after

horsetails and which was sister group to seed plants. Our results

strongly

supported monophyly of the conifers-Ginkgo-cycads clade, where conifers

were

sister group to Ginkgo and cycads. The various phylogenies suggested an

early

divergence of the seed plant lineage leading to Ephedra.



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



*****MUTAGENESIS*****

Horikawa K Mohri T Tanaka Y Tokiwa H

Moderate inhibition of mutagenicity and carcinogenicity of

benzo[a]pyrene,

1,6-dinitropyrene and 3,9-dinitrofluoranthene by Chinese medicinal herbs.

In: Mutagenesis (1994 Nov) 9(6):523-6

ISSN: 0267-8357



The activity of six Chinese medicinal herbs against the environmental

mutagens

and carcinogens benzo[a]pyrene (B[a]P), 1,6-dinitropyrene (1,6-diNP) and

3,9-dinitrofluoranthene (3,9-diNF) was determined. Samples of Prunella

spica,

Rheum palmatum, Polygonum multiflorum, Agrimonia pilosa, Ephedra sinica

and

Teitoutou were tested in an in vitro system. Antimutagenic activity

against

B[a]P was marked in the presence of extracts (boiled for 2 h in a water

bath)

whereas that against 1,6-diNP and 3,9-diNF varied from 20 to 86%. The

differences in inhibition might be due to inactivation of metabolic

enzymes. An

extract of P. multiflorum was divided into ether, ethyl acetate and water

soluble fractions, which were tested for antimutagenic activity against

B[a]P.

The antimutagenic action of the ethyl acetate soluble fraction was

substantial

and dose-dependent. Tannins and related compounds were the major

components of

the extract, of which epigallocatechin, epigallocatechin gallate,

epicatechin

gallate and tannic acid strongly inhibited the mutagenicity of B[a]P (2.5

micrograms/plate) in Salmonella typhimurium TA98 with S9 mix. To confirm

the

results of the in vitro test system, F344/DuCrj male rats were given a

subcutaneous injection of B[a]P. Thereafter, they received water extracts

of the

six Chinese medicinal herbs for 50 weeks and were examined for tumors.

The P.

multiflorum extract significantly reduced the tumor incidence.

Registry Numbers:

22506-53-2 (3,9-dinitrofluoranthene)

42397-64-8 (1,6-dinitropyrene)

50-32-8 (Benzo(a)pyrene)



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



*****TOXICOLOGY LETTERS*****

Tricker AR Wacker CD Preussmann R

2-(N-nitroso-N-methylamino)propiophenone, a direct acting bacterial

mutagen

found in nitrosated Ephedra altissima tea.

In: Toxicol Lett (1987 Sep) 38(1-2):45-50

ISSN: 0378-4274



A new N-nitroso compound identified in a nitrosated tea extract made from

the

plant Ephedra altissima and shown to be formed under in vivo conditions

was

identified as 2-(N-nitroso-N-methylamino)propiophenone (NMAP).

N-Nitrosoephedrine (NEP), another N-nitroso compound detected in

nitrosated

Ephedra altissima tea and NMAP are shown to exert mutagenic activity in

the

Salmonella/mammalian microsome mutagenicity (Ames) test. Base-pair

substitution

mutation-detecting strains (TA100 and TA1535) showed both compounds to be

weak

direct-acting mutagens without the addition of S9-mix. The

identification,

synthesis and mutagenicity of NMAP are discussed.



Registry Numbers:

110505-04-9 (2-(N-nitroso-N-methylamino)propiophenone)

17608-59-2 (N-nitrosoephedrine)



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



*****YAKUBUTSU, SEISHIN, KODO [JAPANESE JOURNAL OF

PSYCHOPHARMACOLOGY]*****

Furuya I Watanabe S

[Discriminative stimulus properties of ephedra herb (Ephedra sinica) in

rats]

In: Yakubutsu Seishin Kodo (1993 Feb) 13(1):33-8

ISSN: 0285-5313 (Published in Japanese)



The stimulus properties of ephedra herb (drug of Chinese medicine) were

demonstrated in rats trained to discriminate between 2.5 ml/kg extract of

ephedra herb and same volume of distilled water (p.o.). On the

discrimination

training, animals were shaped on an FR20 schedule to respond to one of

two

levers for food reinforcement when they were administrated ephedra herb

extract,

and to respond to the other lever when they were treated with distilled

water.

Cumulative dosing tests for the discriminative stimulus properties

consisted of

two to five trials of FR20 schedule; responses for both levers were

reinforced.

d- Methamphetamine 1.43 mg/kg p.o. indicated complete generalization to

the

ephedra herb. Nicotine and caffeine indicated modest generalization, but

some

animals generalized completely. These results suggest that the ephedra

herb has

d-methamphetamine-like, but unique discriminative stimulus properties.



Registry Numbers:

537-46-2 (Methamphetamine)

54-11-5 (Nicotine)

58-08-2 (Caffeine)



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



*****YAKUGAKU ZASSHI. JOURNAL OF THE PHARMACEUTICAL SOCIETY OF

JAPAN*****

Nikaido T Iizuka S Okada N Kuge T Ohmoto T

[The study of Chinese herbal medicinal prescription with enzyme

inhibitory

activity. VI. The study of makyo-kanseki-to with adenosine 3',5'-cyclic

monophosphate phosphodiesterase]

In: Yakugaku Zasshi (1992 Feb) 112(2):124-8

ISSN: 0031-6903 (Published in Japanese)



A Chinese herbal medicinal prescription, Makyo-kanseki-to, was studied

for the

inhibitory activity of adenosine 3',5'-cyclic monophosphate (cAMP)

phosphodiesterase. The effect for the inhibitory activity of cAMP

phosphodiesterase by combination with constituent crude drugs of the

prescription was studied. Gypsum acted as a mitigatory component for

Ephedra

herb and Glycyrrhiza in cAMP phosphodiesterase inhibition test.



Registry Numbers:

EC 3.1.4.17 (3',5'-Cyclic-Nucleotide Phosphodiesterase)



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



Nikaido T Ohmoto T Kuge T Yanagisawa A Teinozawa K Takeda H

Tsukamoto H

[The study on Chinese herbal medicinal prescription with enzyme

inhibitory

activity. III. The study of mao-to with adenosine 3',5'- cyclic

monophosphate

phosphodiesterase]

In: Yakugaku Zasshi (1990 Jul) 110(7):504-8

ISSN: 0031-6903 (Published in Japanese)



Mao-to, a Chinese herbal medicinal prescription was studied for the

inhibitory

activity of adenosine 3',5'-cyclic monophosphate (cAMP)

phosphodiesterase. The

inhibitory activity for this enzyme depended mainly on Ephedra herb and

Glycyrrhiza in this prescription. Apricot kennel acted as a mitigatory

component

for Ephedra herb in cAMP phosphodiesterase inhibitory test. In ephedrine

and the

related compounds the inhibitory activity of cAMP phosphodiesterase was

not

shown.



Registry Numbers:

EC 3.1.4.17 (3',5'-Cyclic-Nucleotide Phosphodiesterase)



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



*****YAO HSUEH HSUEH PAO [ACTA PHARMACEUTICA SINICA]*****

Cui JF Niu CQ Zhang JS

[Determination of six Ephedra alkaloids in Chinese Ephedra (Ma Huang) by

gas

chromatography]

In: Yao Hsueh Hsueh Pao (1991) 26(11):852-7

ISSN: 0513-4870 (Published in Chinese)



Six Ephedra alkaloids, namely ephedrine, pseudoephedrine, norephedrine,

norpseudoephedrine, methylephedrine and methylpseudoephedrine, in 12

species of

Chinese Ephedra were successfully separated and determined by gas

chromatography

with the highly specific and sensitive nitrogen phosphorus detector

(GC/NPD).

The column used (HP-5) had a cross linked 5% phenylmethylsilicone phase.

Diphenylamine was used as the internal standard to check the

reproducibility of

the extraction yields of the alkaloids, the stability of the detector

response

and to quantify the alkaloids. The contents of the six alkaloids were

calculated

according to their regression equations. The way for the preparation of

crude

drug samples was improved, the diethyl ether extract of the alkalized

crude

sample was directly analysed by GC. The method is simple, rapid and

sensitive.

The results are in agreement with those of the HPLC method.



Registry Numbers:

14838-15-4 (Phenylpropanolamine)

17605-71-9 (N-methylephedrine)

299-42-3 (Ephedrine)

36393-56-3 (norpseudoephedrine)



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



Zhang JS Li SH Lou ZC

[Morphological and histological studies of Chinese Ephedra, ma huang. II.

Species produced in southwestern China and other species]

In: Yao Hsueh Hsueh Pao (1990) 25(1):54-65

ISSN: 0513-4870 (Published in Chinese)



In this paper, the morphological and histological characters of crude

drugs

derived from Ephedra likiangensis Florin, E. likiangensis f. mairei

(Florin) C.

Y. Cheng, E. saxatilis Royle ex Florin, E. gerardiana Wall, E. gerardiana

var.

congesta C. Y. Cheng, E. minuta Florin, E. minuta var. dioeca C. Y.

Cheng, E.

lepidosperma C. Y. Cheng, E. lomatolepis Schrenk and E. intermedia var.

tibetica

Stapf are described, compared and illustrated with line drawings. It was

found

that all the Ephedra spp. growing in southwester nChina possess the

following

features in common, viz. (1) numerous distinct longitudinal ridges are

present

on the stem; (2) xylem fibres and tracheids possess steep, tertiary

spiral

thickenings; (3) stone cells (sclereids) are absent from the nodes.

According to

the above characters, the drugs produced in southwestern China can be

differentiated from those produced in northern China. The results also

show that

the histological characters of E. intermedia var tibetica Stapf produced

in

southeast ern Xizang (Tibet) are different from those produced in north

western

Xizang. The former possesses the xylem fibres and tracheids with steep,

tertiary

spiral thickenings, while the latter possesses sclereids at stem-nodes.

It may

be related to their habitat factors and interspecies hybridization. A key

for

identification of all the crude drugs derived from Chinese Ephedra spp.

studied

in this series of paper, including thirteen species, three varieties and

one

form is presented.



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



Zhang JS Li SH Lou ZC

[Morphological and histological studies of Chinese Ephedra mahuang. I.

Seven

species produced in north China]

In: Yao Hsueh Hsueh Pao (1989) 24(12):937-48

ISSN: 0513-4870 (Published in Chinese)



The Chinese drug Ma Huang, Herba Ephedrae, is well known in the East and

West.

The botanical origin specified in the Chinese Pharmacopoeia (1985

edition)

includes the dried herbaceous stems of Ephedra sinica Stapf, E.

equisetina Bunge

and E. intermedia Schrenk ex Mey. A survey of the botanical origin of

this drug,

however, revealed that other Eqhedra spp. are also used in certain

districts in

China. In order to find means for the identification of drugs derived

from

different plant origins, it is necessary to make a comparative study of

the

morphology and histology of all the Eqhedra spp. growing in China. In

this

paper, the morphological and histological characters of the crude drugs

derived

from the Eqhedra spp. chiefly growing in north China, viz. E. sinica

Stapf, E.

equisetina Bunge, E. intermedia Schrenk ex Mey., E. qrzewaskiistaqs E.

monosperma Gmel. ex Mey., E. fedtschenkoae Pauls, and E. regeliana Florin

are

described, compared and illustrated with line drawings. It is discovered

that

the following characters are useful for their differentiation, viz. (1)

the

presence, shape and height of cuticular papillae of the stem; (2) the

presence,

amount and arrangement of sclereids at stem-nodes; (3) vessels and

tracheids

with bordered pits and spiral thickenings, tracheids with bordered pits

and

reticulate thickenings, and xylem parenchyma cells with reticulate

thickenings,

(4) the ratios of longitudinal and transverse diameters of stomata on the

epidermis of stem and leaf. Observation with scanning electron microscope

(SEM)

revealed that the perforations of the end walls of vessel element in

Eqherda

spp. are bordered. It is also found that the degree of lignification of

fibres

and medullary cells of the herbaceous stems is related to the positions

and

diameters of the stems. It is therefore unsuitable as a diagnostic

feature for

the differentiation of Eqhedrra species.

€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



Zhang JS Tian Z Lou ZC

[Quality evaluation of twelve species of Chinese Ephedra (ma huang)]

In: Yao Hsueh Hsueh Pao (1989) 24(11):865-71

ISSN: 0513-4870 (Published in Chinese)



The contents of six Ephedra alkaloids, namely ephedrine, pseudoephedrine,

norephedrine, norpseudoephedrine, methylephedrine and methyl-

pseudoephedrine, in

12 species of Chinese Ephedra collected in 24 districts were determined

by high

performance liquid chromatography (HPLC). Zorbax CN column (25 cm x 4.6

mm I.D.)

was used and the temperature of column oven was 23-25 degrees C.

Dibutylamine

phosphate solution 0.0009 mol/L (pH 2.2) was used as the mobile phase at

flow

rates: 0.8 ml/min for the first 7 minutes, raised to 1.5 ml/min in 30 sec

and

maintained for 16 minutes. The alkaloids eluted were detected at wave-

length 210

nm. The results showed that ephedrine and pseudoephedrine are the main

components in these Ephedra herbs, but the contents of the six Ephedra

alkaloids

vary greatly with the plant species. The contents of total alkaloids are

higher

and ephedrine is the main component in samples derived from Ephedra

sinica, E.

equisetina, E. monosperma and E. intermedia var. tibetica; but in E.

intermedia

and E. lomatolepis, the content of pseudoephedrine is higher than that of

ephedrine. Methylephedrine content is higher in E. intermedia var.

tibetica

produced in Xizang (Tibet) and in E. sinica produced in north-eastern

China than

that in other species. The results also showed that the samples derived

from E.

przewalskii and E. lepidosperma contain so little alkaloids (less than

0.1%)

that they are considered not suitable to be used as the drug Ma Huang. It

is of

interest that the cultivated Ephedra sinica showed lower alkaloids

content

compared with that growing wild.



Registry Numbers:

14838-15-4 (Phenylpropanolamine)

299-42-3 (Ephedrine)

36393-56-3 (norpseudoephedrine)



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



Shao G Wu F Wang DS Zhu R Luo X

Quantitative analysis of (l)-ephedrine and (d)-pseudoephedrine in plasma

by

high-performance liquid chromatography with fluorescence detection.

In: Yao Hsueh Hsueh Pao (1995) 30(5):384-9

ISSN: 0513-4870



Quantitative analysis of (l)-ephedrine (l-Ep) and (d)-pseudoephedrine (d-

Ps) in

plasma by high-performance liquid chromatography (HPLC) is described. The

newly

developed method is based on a precolumn derivatization with

5-dimethyl-aminonaphthalene-1-sulfonyl chloride (DNSC1) in acetonitrile.

The

diastereomers formed were separated on a reversed phase column by HPLC

with

fluorescence detection employing 0.6% phosphate buffer (pH 6.5)-methanol

(3:8,

v/v) as mobile phase. The detection limit of each Ephedra alkaloid

stereoisomer

was 0.5 ng at a signal-to-noise ratio of 3:1, the linear response to each

stereoisomer being 1-800 ng.ml-1. The plasma level profile of l-Ep and d-

Ps in

guinea pig was investigated by this method. The determination of l-Ep and

d-Ps

in plasma of a volunteer after oral administration of Xiao Qinglong Heji

was

also performed.



Registry Numbers:

299-42-3 (Ephedrine)



€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€



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