Learning Outcome

At the end of the topic, students should be able to:

ü Describe quality, safety and efficacy of a Malay and Indonesian herbal products

üDescribe methods involved in determining the quality, safety, and efficacy of Malay and Indonesian herbal products

List some examples of Malaysian and Indonesian Herb?

QUALITY, SAFETY AND EFFICACY

Why the safety, efficacy, quality is importance?

EXAMPLES OF CERTIFICATE OF ANALYSIS (COA) OF HERBAL PRODUCTS

Quality can be defined as the status of a drug that isdetermined by identity, purity, content and other chemical,physical or biological properties or by the manufacturingprocess

*Maintaining the quality of herbal products is very importantbecause it will effect the safety and effectiveness of theproducts.

FLOW OF QUALITY CONTROL PROCESS

ANTI MICROBIAL

PHYSICAL INSPECTION

SAMPLING FOR ANALYSIS AND

GRINDING

LABORATORY ANALYSIS

CHEMICAL SCREENING LIMIT TESTS GRAVIMETRY

TLC HPLC GC-Znose MICROBIAL HEAVY METAL EXTRAC. VAL. ASH

ANTI OXIDANT CRYSTAL INHIBITION

SAMPLES FROM SUPPLIER (DRIED

LEAVES)

Efficacy & Standardization

Efficacy§ The effectiveness of the herbal extract to address specific claims§ Active contents of herbs vary with planting, harvesting, processing,

packaging and storage§ Efficacy depends on the phytochemical concentration and profile

Standardization§ Standardized herbal extract is an extract within a specified range of

a certain phytochemical or with a specified phytochemical profile§ Standardization ensures herbal efficacy and correct dosages§ Currently available standardized extracts Ginseng G115, Gingko

Biloba Egb 761

SAFETY

Safety§ Dosages which are toxic

• Some herbs can only be taken in very small doses such as Kava• Some herbs are non toxic at extremely high doses such as Ginseng

and Ganoderma

§ Counter indications and drug interactions• Many herbs cannot be taken with heart medicine I.e wafarin, and

pressure medicine i.e Norvask due to diuretic and metabolic change herb effects

• Bad reactions such as yellowing of skin from excess Kava should be labeled

SAFETY ISSUES: Adverse Effects

• Contamination• Adulteration• Actions of herb itself• Herb-drug interaction

– Interference with anesthesia– Interference with clinical effects of drugs

Dr Ismail Merican

Control of Drugs and Cosmetic Regulation 1984

Sales of Drug Act 1952 (revised 1989)

Registration of herbal products (1992)

Good Manufacturing practices

Licensing of herbal medicine importers (1999)

Source: Dr Ilham,FRIM

TRADITIONAL/ HERBAL MEDICINES LAWS & REGULATION

The Star 7 Sept 2003

QUALITY

UV VIS SPECTROPHOTO

METER

TLCHPLC

GC

METHODS IN DETERMINE QUALITY OF HERBAL PRODUCTS

High Performance Liquid Chromatography (HPLC)

THIN LAYER CHROMATOGRAPHY (TLC)

Gas Chromatography (GC)

Quality Evaluation Of Orthosiphon stamineus Products

1) DETERMINE MARKER COMPOUND IN O. stamineus Tea USING HPLCØ Rosmarinic acid (RA)ØSinensitin (SIN)ØEupatorinMobile Phase: MeOH:H2O:Tetrahydrofuran (45:50:5 v/v)Detector: UV DetectorResult: Chromatogram of O. stamineus Tea

1 2 3 4 5 6 7 8 9 10 11 12

TLC CHROMATOGRAMS OF Orthosiphon stamineus

1- RAWANG, SELANGOR 5- KEPALA BATAS, P. PINANG 9- NUSANTARA HERBS

2- BOHOR TEMAK, PERLIS 6- MARDI BACHOK, KELANTAN 10- MEDAN, SUMATERA

3- BUMBUNG LIMA, P. PINANG 7- SARAWAK 11- PADANG, SUMATERA

4- BOTA KANAN, PERAK 8- KUALA NERANG, KEDAH 12- SINENSETIN

TLC PROFILE OF LEAVES OF B. BALSAMIFERA & CHEMICAL MARKERS (FLAVANONE)

Note:Solvent SystemCHCl3:MeOH(9:1)

Rf ValuesBLM-5 : 0.305BLC-1 : 0.470

Spraying Reagents1% methanolicdiphenylboricacid-β-ethylaminoester.

BLM5

BLC1

BLM5 BLM5

BLC1 BLC1

Under UV(254 nm)

Under UV(365 nm) Day light

SAFETY

MLT HEAVY METAL ANALYSIS

METHODS IN DETERMINE SAFETY OF HERBAL PRODUCTS

ATOMIC ABSORPTION SPECTROSCOPY (AAS)

AAS DATA

0

1000

2000

3000

4000

ppb

Screening Heavy Metal (AAS) - Raw Material

Pb < 10000 ppb 1590 1574 1557.5 3582 3561 3512.5 3117.5

As < 5000 ppb 868 786 409.5 1256.5 1169 1268 1036.5

Cd < 300 ppb 163.5 106.5 115.5 205.5 138.5 156 116.5Hg < 500 ppb 107.5 125 64.5 286.5 222 234 94.5

NNPPDM01

NNPPDM03

NNPPDM04

SRKBPM06

SRKBPM07

SRKBPM07-k1

STJGCM-01 0

1000

2000

3000

4000

5000

6000

ppb

Screening Heavy Metal (AAS) - Extract

Pb < 10000ppb 5702.5 2229.5 3925 1067.5 2962.5 1747.5 904

As < 5000 ppb 2169 1765.5 2256.5 768 986 429.5 336.5

Cd < 300 ppb 198.5 166 245.5 153.5 176.5 125.5 84

Hg < 500 ppb 322 286.5 386.5 97.5 135 74.5 66.5

HVMSDE01 HVMSDE02 HVMFDE01 NHISDE02 NHMSDE03 NHICE01-b NHICE01-a

Keputusan ujian kontaminasi logam berat beberapa sampel bahan mentah dan ekstrakMisai Kucing

MICROBIAL LIMIT TEST (MLT)

EFFICACYIN

VITROIN

VIVO

METHODS IN DETERMINE EFFICACY OF HERBAL PRODUCTS

IN VITRO

• Studied that are performed with cell or biological molecule outside their normal biological context

• Called “ Test tube experiment” traditionally done in test tube, petri dish and flasks

• They now involve full range of techniques used in molecular biology such as the so-called omics. Studies that are conducted using components of an organism that have been isolated from their usual biological surrounding permitted more details or more convenient analysis that can be done with whole organisme.

• For example:• Proteins are examined in solution, or cells in artificial culture medium

IN VITRO TEST APPROACH

IN VIVO

• Studied that are conducted in animals including humans and whole plants.

• Often employed over in vitro because it is better suited for observing the overall effects of an experiments of living subjects

For example:• Pathogenesis of disease by comparing the effects of bacterial

infection with the effect of purified bacterial toxin- development of antibiotics, antiviral drugs and new drugs

• Clinical trials and animal testing

QUESTIONS

1- Give four main issues in safety of herbal products?2- State the method used to determine quality of herbal products?3- State the method used to determine safety of herbal products?4- State the method used to determine efficacy of herbal products?

Answer the question in the small paper given and submit to the lecturer before exit the class