🇲🇾 NPRA — Pusat Kawalan Kualiti · ISO/IEC 17025 Accredited

◈ Seksyen Pengujian Produk & Kosmetik · Unit Penyaringan

PKKK/300/UP/047 Screening of Theophylline & Caffeine in Cosmetic Samples using GCMS

Arahan Kerja Rasmi (Level 300 SOP) · Kategori: GC-MS

1. Reagen & Piawai

Penyediaan fasa bergerak, stok & kalibrasi

➔

2. Pengekstrakan

Timbang, sonikasi, sentrifug & turas 0.45µm

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3. Persediaan Alat

Purging saluran, autotune & baseline

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4. Suntikan Batch

Blank, SST (n=6), Sampel & IQC

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5. Verifikasi & Rekod

Padanan RT, spektrum UV/MS & Laporan

⚡ Spesifikasi & Parameter Kromatografi / Analitikal (Official Parameters):

Instrumen UtamaAgilent / Shimadzu GC-MS Systems

Turus / ColumnHP-5MS / Rtx-5MS (30 m × 0.25 mm × 0.25 µm)

Fasa Bergerak / PelarutHelium Gas Pembawa @ 1.0 mL/min

Kadar Alir & SuhuSplit 20:1 @ 250 °C @ Oven: 80 °C (1 min) → 15 °C/min ke 280 °C (5 min)

Pengesan / Gelombang / SIMEI 70 eV · Scan m/z 40 – 450 amu

Kriteria Kesesuaian Sistem (SST)Padanan spektrum Theophylline (m/z 180, 95) & Caffeine (m/z 194, 109) > 800.

🎯 Sebatian Sasaran Pengujian:

TheophyllineCaffeine

💡 Petua & Perhatian Penting Makmal (Bench Notes):

Lakukan Standard Spectra Tune (s.tune) atau Autotune (a.tune) setiap hari sebelum analisis dan pastikan laporan LULUS.
Semak paras kebocoran udara/air (Air/Water Check): m/z 18 < 10% dan m/z 28 < 5% berbanding puncak dasar m/z 69.
Gunakan pelarut berkualiti kromatografi gas dan pastikan septum suntikan ditukar berkala bagi mengelak 'ghost peaks'.

Analyst Benchtop Checklist Progress

0 / 10 Langkah Selesai (0%)

NPRA PUSAT KAWALAN KUALITI	ARAHAN KERJA: SCREENING OF THEOPHYLLINE & CAFFEINE IN COSMETIC SAMPLES USING GCMS
	No. Dokumen: PKKK/300/UP/047	Terbitan / Semakan: Terbitan 3 Semakan 0
	Tarikh Kuatkuasa: 10 April 2026	Bahagian / Unit: SPPK · Unit Penyaringan

0.0 SEJARAH PINDAAN & SEMAKAN 1.0 OBJECTIVE 2.0 SCOPE 4.0 FLOW CHART 5.0 RESPONSIBILITIES 6.0 PROCEDURE 7.0 QUALITY RECORDS 8.0 ATTACHMENTS 📊 Jadual Data (4)

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0.0 SEJARAH PINDAAN & SEMAKAN

AMENDMENT :

This procedure is a new document in line with upgrading the institution’s certification to the ISO 9001: 2015 version and the renaming of the institution from National Pharmaceutical Control Bureau (NPCB) to Bahagian Regulatori Farmasi Negara (NPRA). Therefore, the original document is obsolete and this document is published as Version 1.

HISTORY OF REVISION :

Issue 2 Revision 0 :

Update on document number from PKK/200/KOS/009 to PKK/200/HMS/001

Update on effective date from 15 November 2016 to 10 February 2020

Update on responsibility.

Issue 3 Revision 0 :

Document change from testing procedure PKK/200/HMS/001 to work instruction PKK/300/HMS/056

Issue 3 Revision 1 :

i. Update on name of agency from National Pharmaceutical Regulatory Agency (NPRA) to Bahagian Regulatori Farmasi Negara (NPRA)

Issue 4 Revision 0 :

Update document number from PKK/300/HMS/056 to PKKK/300/HMS/056

Update on list of references

Update paragraph 5.0 Responsibilities

Update paragraph 6.4 Evaluation

Update paragraph 7.0 Quality Records

Issue 5 Revision 0 :

Update document number from PKKK/300/HMS/056 to PKKK/300/KOS/015

Update paragraph 5.0 Responsibilities

Update paragraph 7.0 Quality Records

Issue 5 Revision 1 :

Update document number from PKKK/300/KOS/015 to PKKK/300/UP/047.

Update effective date from 1 April 2024 to 10 April 2026

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1.0 OBJECTIVE

◼ To screen for theophylline & caffeine present in cosmetic samples using GCMS.

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2.0 SCOPE

◼ This test method is only to be used for identification of theophylline & caffeine in cosmetic products.

3.0 Definition

3.1 GCMS : Gas Chromatography Mass Spectrometry

3.2 EI : Electron Ionisation

3.3 Analyst : Pharmacist/Pharmacy assistant/Science Officer

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4.0 FLOW CHART

▹ - None -

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5.0 RESPONSIBILITIES

Head of Section

5.1.1 Validate analysis report of failed sample and approve on QUEST System

Head of Unit / Pharmacist in Charge

Distribute samples for testing to Pharmacist through QUEST system

Validate and approve analysis report on QUEST system

Review investigation report of failed samples

Pharmacist

Distribute samples for testing among analysts

Ensure tests are conducted according to laboratory protocols

Review analysis reports and update into the QUEST system

Investigate and report failed samples

Perform sample analysis (when necessary) and report

Pharmacy assistant

Perform sample analysis and report

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6.0 PROCEDURE

6.1 Equipment/ Materials

◼ GCMS – QP 2010

GC Column : Rxi – 5Sil MS 30m x 250mm x 0.25µm

◼ Ultrasonic bath

◼ Glass stoppered conical flasks

◼ Volumetric flask (20 mL)

◼ Glass fiber filter paper (125 mm)

◼ GC autosampler vial

◼ Ethanol

◼ Theophylline Reference Standard

Caffeine Reference Standard

Test Method

Standard preparation

Reference solution: 0.1 mg/mL of Theophylline and Caffeine in Ethanol.

Accurately weigh 2.0 mg of Theophylline Reference Standard and Caffeine reference standard and put it in a 20 mL volumetric flask. Make up to volume with Ethanol.

Note: The weight of reference standard can be modified to minimize the usage of the reference standard.

Sample preparation

Langkah 1 Weigh about 0.5 g sample into a glass stoppered conical flask, add 20 mL Ethanol. Sonicate until it dissolves. Pipette 1 mL of sample solution into 10 mL volumetric flask and make up to volume with Ethanol.

Langkah 2 Filter through a 125mm glass fiber filter paper into a GC autosampler vial.

Use the filtrate for GCMS injection

Chromatographic Conditions

GCMS Conditions:

Mode : EI

Injection volume : 1 μL

Split ratio : 10:1

Column flow : 1.0mL/min

Inlet temperature : 250°C

Interface temperature : 280°C

MS Quad temperature : 150°C

MS source temperature : 230°C

Oven temperature:

Langkah 3 Run time : 32 – 50 min

Langkah 4 Inject the reference solution and sample preparation into GCMS.

Evaluation

From the chromatogram of the sample, a compound is reported as detected (positive) should the retention time and mass spectrum match between the sample and reference standard with more than 80 % similarity. The principal ions for the compounds are :

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7.0 QUALITY RECORDS

Borang Tatacara Pengujian menggunakan kaedah : UP/X015

GCMS

Rumusan Laporan Pengujian Kromatografi : UP/009

Laporan Siasatan Sampel Kosmetik Tidak Lulus Ujian Kromatografi : UP/002B

Keputusan Ujian Kosmetik : UP/X013

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8.0 ATTACHMENTS

Chromatogram and mass spectrum of Reference Standard Theophylline & Caffeine.

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Jadual Kromatografi & Rujukan Data

JADUAL 1 PKKK/300/UP/047

HISTORY OF REVISION	HISTORY OF REVISION	HISTORY OF REVISION	HISTORY OF REVISION	HISTORY OF REVISION	HISTORY OF REVISION
Issue	Revision	Written by	Reviewed by	Approved by	Effective date
1	0	Nor Izyani Hanafi	Ooi Suat Hong	Dr Noraida Mohd Zainoor	15 November 2016
2	0	Nor Izyani Hanafi	Ooi Suat Hong	Wan Nurul Aina Mior Abdullah	10 February 2020
3	0	Nor Izyani Hanafi	Ooi Suat Hong	Wan Nurul Aina Mior Abdullah	15 Julai 2020
3	1	Nor Izyani Hanafi	Ooi Suat Hong	Wan Nurul Aina Mior Abdullah	15 Disember 2020
4	0	Gopinatha Ganesh	Nor Izyani Hanafi	Wan Nurul Aina Mior Abdullah	1 November 2022
5	0	Leong Lip Wai	Gopinatha Ganesh	Nor Izyani Hanafi	1 April 2024
5	1	Nurul Nadiah Noh	Gopinatha Ganesh	Ida Syazrina Ibrahim	10 Apr 2026

JADUAL 2 PKKK/300/UP/047

REFERENCES	REFERENCES
Document No.	Title
	Suggested in ASEAN Working Group on Technical Cooperation in Pharmaceuticals (AWGTCP) Meeting in Kuala Lumpur, on – May 2006
	Standard Operating Procedure for GCMS
	Clarke’s Analysis of Drugs and Poisons, Fourth Edition

JADUAL 3 PKKK/300/UP/047

Oven Ramp	°C/min	Next °C	Hold min
Initial		100°C	2 min
Ramp 1	20	200°C	5 min
Ramp 2	20	260°C	5 min
Ramp 3	20	280°C	5 min
Ramp 4	20	310°C	5 min

JADUAL 4 PKKK/300/UP/047

No	Compound	Principal ions (m/z)
1.	Theophylline	180, 95, 68, 41, 53, 181, 96, 40
2.	Caffeine	194, 109, 55, 67, 82, 195, 42, 110