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

◈ Seksyen Pengujian Produk & Kosmetik · Unit Penyaringan

PKKK/300/UP/048 Identification of Hydroquinone in Cosmetic Products 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

➔

3. Persediaan Alat

Purging saluran, autotune & baseline

➔

4. Suntikan Batch

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

➔

5. Verifikasi & Rekod

Padanan RT, spektrum UV/MS & Laporan

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

Instrumen UtamaAgilent 8890 GC-MS System

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

Fasa Bergerak / PelarutHelium Gas Pembawa @ 1.0 mL/min

Kadar Alir & SuhuSplit 10:1 @ 250 °C @ Oven: 70 °C (1 min) → 12 °C/min ke 250 °C (4 min)

Pengesan / Gelombang / SIMMS EI 70 eV · Scan / SIM m/z 110, 81, 53

Kriteria Kesesuaian Sistem (SST)RT match ±2%, ion ratio match had toleransi Table 6.

🎯 Sebatian Sasaran Pengujian:

Hydroquinone

⚙️ SOP Pengendalian Alat Yang Digunakan Untuk Ujian Ini:

PKKK/300/UP/040

GCMS Shimadzu QP2010 Ultra

Buka Panduan Alat →

PKKK/300/UP/017

GCMS Agilent 8890 / 5977B

Buka Panduan Alat →

PKKK/300/UP/005

Alat Timbang Precisa XT 120A

Buka Panduan Alat →

💡 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 / 9 Langkah Selesai (0%)

NPRA PUSAT KAWALAN KUALITI	ARAHAN KERJA: IDENTIFICATION OF HYDROQUINONE IN COSMETIC PRODUCTS USING GCMS
	No. Dokumen: PKKK/300/UP/048	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 6.0 PROCEDURE 7.0 QUALITY RECORDS 8.0 ATTACHMENTS 📊 Jadual Data (3)

📋

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 National Pharmaceutical Regulatory Agency (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/013 to PKK/200/HMS/002

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/002 to work instruction PKK/300/HMS/057

Issue 4 Revision 0 :

Update document number from PKK/300/HMS/057 to PKKK/300/HMS/057

Update on List of References

Update on para 6.1 Equipment/Materials

Update on para 6.2 Chromatographic Parameters

Update on para 6.3.2 Sample Preparation

Update on para 6.4 Results

Issue 4 Revision 1 :

Update para 6.4 Results

Issue 5 Revision 0 :

Update document number from PKKK/300/HMS/057 to PKKK/300/KOS/016

Update paragraph 5. Responsibility

Issue 5 Revision 1 :

Update paragraph 6.3.1 Reference standard preparation

Issue 6 Revision 0 :

Update document number from PKKK/300/KOS/016 to PKKK/300/UP/048.

Update effective date from 1 April 2024 to 10 April 2026

🎯

1.0 OBJECTIVE

◼ To identify the presence of hydroquinone in cosmetic products using GC-MS.

📐

2.0 SCOPE

◼ This test method is only to be used for identification of hydroquinone in cosmetic products which is suspected to contain the substance.

3.0 Definition

3.1 GCMS : Gas Chromatography Mass Spectrometry

3.2 EI : Electron Ionisation

3.3 Analyst : Pharmacist/Pharmacy assistant/Science Officer

🔀

4.0 FLOW CHART

▹ - None -

Responsibility

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

Analyst

Perform sample analysis and report

🔬

6.0 PROCEDURE

6.1 Equipment/ Materials

GCMS – QP 2010

Ultrasonic bath

Glass conical flasks with screw cap

Volumetric flask (20 mL)

Nylon filter, 47 mm diameter, 0.45 µm pore size or equivalent

GC autosampler vial

Methanol

Hydroquinone Reference Standard

Chromatographic Parameters

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

◼ Oven temperature:

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

Gas : Helium

Test Method

Reference Standard Preparation

Langkah 1 Weigh accurately 2 mg of Hydroquinone Reference Standard and put it in a 20 mL volumetric flask. Make up to volume with Methanol. Pipette 3 mL of standard solution into 10 mL volumetric flask and make up to volume with Methanol. Filter the solution before injecting into the GCMS. (0.03 mg/mL)

Note: The concentration of reference standard can be modified according to the system response during analysis.

Sample Preparation

Langkah 2 Weigh accurately 0.5 g of sample into a glass conical flask. Add in 20 mL of Methanol. Sonicate until it dissolves. Pipette 1 mL of sample solution into 10 mL volumetric flask and make up to volume with Methanol. Filter the solution before injecting into the GCMS.

Note: Further dilution of sample can be done if the concentration of sample is too high.

Measurement

Langkah 3 Inject 1 μL of Reference Standard solution and sample preparation into the GCMS and check the chromatogram.

Results

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 hydroquinone are 110, 53, 39, 54 and 82.

📝

7.0 QUALITY RECORDS

Borang Tatacara Pengujian menggunakan kaedah : UP/X015

GCMS

Laporan Siasatan Sampel Gagal (Analyst) : UP/002A

Keputusan Ujian Kosmetik : UP/X013

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

📎

8.0 ATTACHMENTS

Chromatogram and mass spectrum of Reference Standard Hydroquinone

📊

Jadual Kromatografi & Rujukan Data

JADUAL 1 PKKK/300/UP/048

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 Mohamad 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 July 2020
4	0	Gopinatha Ganesh	Nor Izyani Hanafi	Wan Nurul Aina Mior Abdullah	1 November 2022
4	1	Gopinatha Ganesh	Nor Izyani Hanafi	Wan Nurul Aina Mior Abdullah	1 April 2023
5	0	Leong Lip Wai	Gopinatha Ganesh	Nor Izyani Hanafi	1 April 2024
5	1	Leong Lip Wai	Gopinatha Ganesh	Nor Izyani Hanafi	1 Julai 2024
6	0	Nurul Nadiah Noh	Gopinatha Ganesh	Ida Syazrina Ibrahim	10 April 2026

JADUAL 2 PKKK/300/UP/048

REFERENCE	REFERENCE
Document No.	Title
	Standard Operating Procedure for GCMS
	Notes on ‘GCMS in Biomedical Analysis’
	Notes on HP GCMS
	Clarke’s Analysis of Drugs and Poisons, Fourth Edition
	National Library of Medicine (PubChem) website

JADUAL 3 PKKK/300/UP/048

Oven Ramp	°C/min	Next °C	Hold Time (min)	Run Time (min)
Initial		100°C	2
Ramp 1	20	200°C	5
Ramp 2	20	260°C	5
Ramp 3	20	280°C	5
Ramp 4	20	310°C	5
Post Run		100°C	0	32.5