LAPORAN METODE ANALISIS RESIDU

RIFAMPISIN DARI TABLET SALUT SELAPUT

NATRIUM DIKLOFENAK 50 MG

RESIDUE ANALYTHICAL METHOD REPORT

SODIUM DIKLOFENAK FROM SODIUM
DIKLOFENAK 50 MG FILM COATED TABLET
(MA-31-0002-00)

PLANT BANJARAN
PT. KIMIA FARMA (Persero), Tbk
2018
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 2 of 30

LEMBAR PENGESAHAN
Approval Sheet

NAMA PRODUK : Tablet Salut Selaput Natrium Diklofenak 50 Mg/ Diclofenac Sodium
50 Mg Film Coated Tablet
JENIS PEMERIKSAAN : Verifikasi Metode Analisa Residu/ Residue Analytical Method
Verification
PROTOKOL : LAPORAN CLEANING VALIDASI - METODE ANALISIS
RESIDU
NO. PROTOKOL : MA-31-0002-00

Dengan menandatangani halaman ini menngindikasikan persetujuan terhadap verifikasi metode

analisa residu yang ada pada dokumen ini. Setiap perubahan pada proses verifikasi akan dibuatkan
sebagai addendum.
Signing of this page indicates approval with the residue analytica method verification described in
this document. Any modifications of this validation will be prepared and approves as an addendum.

Prepared By
Company Name Designation Signature Date
Cleaning Validation
Officer

Reviewed By
Company Name Designation Signature Date
Head of Project
Validation and
Qualification

Project Manager

Approved By
Company Name Designation Signature Date

QA Manager
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 3 of 30

DAFTAR ISI
I. TUJUAN/OBJECTIVE ........................................................................................................... 4
II. RUANG LINGKUP/SCOPE .................................................................................................... 4
III. ACUAN / REFERENCE ...................................................................................................... 4
IV. TANGGUNGJAWAB/RESPONSIBILITY .................................................................................. 4
V. KEGIATAN VALIDASI/VALIDATION APPROACH .................................................................... 5
5.1 Formula Produk/ Product Formula ................................................................................ 6
5.2 Formula untuk Pemeriksaan/ Formula for Inspection ..................................................... 6
5.3 Formula Sampel Uji/ Sample Formula ........................................................................... 7
5.4 Bahan/ Material ........................................................................................................... 8
5.5 Alat/ Equipment .......................................................................................................... 8
5.6 Kondisi Pengerjaan HPLC / HPLC Working Condition .................................................... 8
5.7 Kriteria Penerimaan/ Acceptance Criteria....................................................................... 9
5.8 Pelaksanaan Validasi/ Implementation of Validation ....................................................... 11
5.8.1 Uji Kesesuaian Sistem / System Suitability Test ................................................. 11
5.8.2 Selektivitas / Selectivity ................................................................................... 12
5.8.3 Akurasi / Accuracy .......................................................................................... 13
5.8.4 Presisi / Precision ............................................................................................ 14
5.8.5 Linearitas dan Rentang / Linearity and Range ................................................... 15
5.8.6 LOD & LOQ (Batas Deteksi & Batas Kuantifikasi) ............................................... 16
5.8.7 Ketegaran/ Robustness.................................................................................... . 18
5.8.8 Sample Recovery ............................................................................................ 25
5.9 Pengolahan Data/ Data Processing ............................................................................ 28
5.10 Evaluasi / Evaluation ............................................................................................... 29
VI. KESIMPULAN/ CONCLUSION ............................................................................................ 30
VII. RIWAYAT REVISI PROTOKOL/ REVISED HISTORY ............................................................... 30

Lampiran / Appendix

1. Resume Validasi Metode Analisa ............................................................................................ 31

2. Verifikasi Status Kualifikasi & Kalibrasi Alat yang Digunakan ..................................................... 32
3. Identitas & Penimbangan Standar dan Bahan Baku ................................................................. 33
4. Pengerjaan Validasi .............................................................................................................. 35
1. Uji Kesesuaian Sistem ..................................................................................................... 35
2. Selektivitas ..................................................................................................................... 36
3. Linearitas & Rentang ....................................................................................................... 39
4. Uji Batas Deteksi & Batas Kuantifikasi ............................................................................... 40
5. Akurasi ........................................................................................................................... 41
6. Presisi ............................................................................................................................ 42
7. Ketegaran ...................................................................................................................... 45
8. Rinse Recovery ............................................................................................................... 46
9. Swab Recovery ............................................................................................................... 47
5. Formulir Penyimpangan ......................................................................................................... 48
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 4 of 30

I. TUJUAN/OBJECTIVE
Untuk membuktikan dan memastikan bahwa metode analisis penentuan jumlah residu Tablet
Salut Selaput Natrium Diklofenak 50 mg dapat selalu memberikan hasil pemeriksaan yang
memenuhi persyaratan yang telah ditetapkan.

To prove and ensure that the analysis method of determining the residual amount of 50 Mg
Diclofenac Sodium Film Coated Tab always provide an inspection result that meets
requirements.

II. RUANG LINGKUP/SCOPE

Metode analisa yang diverifikasi adalah prosedur penetapan jumlah residu Natrium Diklofenak
dari tablet salut selaput Natrium Diklofenak 50 mg yang tertera pada Farmakope Indonesia
Edisi V, 2015

The analytical method has to be verification is procedure of determining the amount of

Diclofenac Sodium residue from Diclofenac Sodium residue50 mg Film Coated Tablet which is
listed on Indonesia Pharmacopeia, Five Edition, 2015

III. ACUAN / REFERENCE

1. Farmakope Indonesia Edisi V, 2015
2. BPOM : “Petunjuk Operasional Penerapan Cara Pembuatan Obat yang Baik Jilid 1”, 2012

1. Indonesia Pharmacopeia, Five Edition, 2015

2. BPOM : “Petunjuk Operasional Penerapan Cara Pembuatan Obat yang Baik Jilid 1”, 2012

IV. TANGGUNGJAWAB/RESPONSIBILITY
4.1 Cleaning Validation officer
4.1.1 Membuat protokol validasi metode analisa residu
4.1.2 Melaksanakan protokol validasi metode analisa residu
4.1.3 Mendokumentasikan data terkait validasi metode analisa residu
4.1.4 Melakukan pelaporan penyimpangan (jika ada)
4.1.5 Mengusulkan & melaksanankan tindakan korektif bila ada penyimpangan
4.1.6 Membuat laporan validasi metode analisa residu
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 5 of 30

4.2 Head of Project Validation and Qualification

4.2.1 Meninjau kesesuaian protokol dan laporan validasi metode analisa residu dengan
VMP
4.2.2 Menyetujui tindakan korektif untuk menanggulangi penyimpangan (jika ada)

4.3 Poject Manager

4.3.1 Meninjau dan menyetujui protokol dan laporan validasi metode analisa residu

4.4 Quality Assurance Manager

4.4.1 Meninjau dan menyetujui protokol dan laporan validasi metode analisa residu serta
memastikan bahwa hal tersebut selaras dengan penerapan sistem manajemen
mutu

4.1 Validation Officer is responsible for :

4.1.1 Prepare Residue Analysis Method Validation Protocol
4.1.2 Execute Residue Analysis Method Validation Protocol
4.1.3 Record Execution Data of Residue Analysis Method Validation
4.1.4 Report Deviation (If any)
4.1.5 Propose and Execute corrective action for deviation
4.1.6 Prepare Residue Analysis Method Validation Report

4.2 Head of Project Validation and Qualification

4.2.1 Review protocol and summary report to ensure that Analysis Method Validation of
Cleaning Residue Protocol Complies with VMP
4.2.2 Approve Corrective action to close deviation (if any)

4.3 Project Manager

4.3.1 Review and approve Analysis Method Validation of Cleaning Residue Protocol and
summary report

4.4 Quality Assurance Manager

4.4.1 Review and approve Analysis Method Validation of Cleaning Residue Protocol and
summary report to ensure that it is aligned with implementation of quality
management system.
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 6 of 30

5 KEGIATAN VALIDASI/VALIDATION APPROACH

Kegiatan validasi yang dilaksanakan adalah validasi metode analisa residu Natrium Diklofenak
dari produk Tablet Salut Selaput Natrium Diklofenak 50 Mg

Impementation of verification activities for verification residue analytical method of Diclofenac

Sodium from Diclofenac Sodium 50 Mg Film Coated Tablet

5.1 Formula Produk/ Product Formula

Formula per tablet salut selaput Natrium Diklofenak dengan bobot 236,783 mg adalah:
The Diclofenac Sodium 50 Mg film coated tablet formula with a weigh 236,783 mg is :
Jumlah Tanggal
No Nama Bahan No LA
(mg) Kadaluarsa
1 Natrii Diclofenac 50
2 Povidonum K-30 8,4
3 Aethenolum 0,028 ml
4 Lactosum 103,31
5 Amylum Maydis 31,484
6 Acidum Sillicum Koloidal 200 4,2
7 Talcum 11,31
8 Magnesii Stearas 1,28
9 Acril Eze 93018359 white 22,222
10 Aquadestilata 0,0888
11 Opadry II 85G58977 white 3,333
12 Pigmen Blend Yellow PB 52153 1,111
13 Aquadestilata 0,0222

5.2 Formula untuk Pemeriksaan/ Formula for Inspection

Formula untuk 20 tablet / Formula for 20 tablets
No Nama Bahan Jumlah (mg)
1 Natrii Diclofenac 1000
2 Povidonum K-30 168
3 Aethenolum 0,572 ml
4 Lactosum 2066,31
5 Amylum Maydis, kering 629,688
6 Acidum Sillicum Koloidal 200 84
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 7 of 30

7 Talcum 226,32
8 Magnesii Stearas 25,68
9 Acril Eze 93018359 white 444,44
10 Aquadestilata 1,776 ml
11 Opadry II 85G58977 white 66,66
12 Pigmen Blend Yellow PB 52153 22,22
13 Aquadestilata 0,444 ml

Cara pembuatan placebo :

Timbang seksama povidonum K-30, aethanolum, lactosum, amylum maydis kering,

acidum sillicum koloidal 200, talcum, magnesii stearas, acril eze 93018359 white, opadry
II 85G58977 white, pigmen blend yellow PB 52153, dan aquadestilata. Gerus dan campur
semua bahan-bahan hingga homogen. Masukkan ke dalam wadah yang telah diberi
identitas. Placebo siap untuk digunakan.

How to make placebo :

Weigh accurately povidonum K-30, aethanolum, lactosum, amylum maydis kering, acidum
sillicum koloidal 200, talcum, magnesii stearas, acril eze 93018359 white, opadry II
85G58977 white, pigmen blend yellow PB 52153, and aquadestilata . Grind and mix all
ingredients untill homogeneous. Put it into an identifiable container. Placebo ready for use.

5.3 Formula Sampel Uji/ Sample Formula(Bobot 1 Tablet = 23.678 mg)

Persen Nama Bahan
No Natrium Jumlah
Jumlah Placebo (mg)
Diklofenak Diclofenac Sodium (mg)
1 80 4 mg 19.678 mg
2 90 4.5 mg 19.178 mg
3 100 5 mg 18.6783 mg
4 110 5.5 mg 18.178 mg
5 120 6 mg 17.678 mg

Preparasi sampel uji :

Timbang seksama Natrium Diklofenak & placebo sesuai tabel diatas dan sampel uji siap
digunakan.
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 8 of 30

Preparation of test sample:

Weigh accurately Diclofenac Sodium& placebo according to the above table and the test
sample is ready for use.

5.4 Bahan/ Material

Baku kerja dan pereaksi yang digunakan meliputi :
Working standars and reagent that used include :
No Nama Bahan Merek/Origin No Lot / LA Tanggal
Kadaluarsa
Baku Kerja Natrium
1
Diklofenak
2 Metanol
3 Asam Fosfat
4 Natrium Fosfat Monobasa
5 Aquadest

Pembuatan Larutan Dapar Fosfat pH 2.5

Campuran Asam Posfat 0.01 M dan Natrium Posfat Monobasa dengan perbandingan 50 :
50. Atur pH hingga 2,5±0,2 dengan penambahan Asam Posfat atau Natrium Hidroksida

Preparation Buffer Phosphat Solution pH 2.5

A mixture of Phosporic Acid 0.01 M and Sodium Phosphat Monobasa with ratio 50:50.
Adjust pH until 2.5±0.2 with a Phosporic Acid or Sodium Hydroxide

5.5 Alat /Equipment

Daftar alat yang digunakan dalam pemeriksaan terdiri dari :
List of tools used in the examination consists of :
No Nama Alat Merek Tanggal Kalibrasi
1 HPLC
2 Kolom L7 (250 x 4.6 mm)
4 Ultrasonic
5 Plat SS 5x5 cm2
6 Labu ukur 50 mL
7 Labu ukur 100 mL
8 Pipet volume 1 mL
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 9 of 30

No Nama Alat Merek Tanggal Kalibrasi

9 Batang Apus
10 Tabung Reaksi
11 Semi-micro analytical balance
12 Micro analytical balance

5.6 Status Baku Standar / Working Standard status

No Uraian Working Standar Bahan Baku
1 Nama Rifampicin Rifampicin Powder
Hebei Xingang
2 Merk Hebei Xingang -China
Pharmaceutical
3 Sertifikat Analisis Ada Ada
4 No Lot C07U1706022 10000026958
5 Tanggal Pembuatan 09 Juni 2017 03 November 2017
6 Tanggal Kadaluarsa 30 Juni 2017 30 November 2021
7 Tanggal Uji 1 Maret 2018 27 Desember 2017
8 Tanggal Uji Ulang 01 Maret 2019 27 Desember 2018
9 Kadar (%) 100,46 % 98,90
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 10 of 30

5.7 Pelaksanaan Validasi/ Implementation of Validation

5.7.1 Uji Kesesuaian Sistem
Detektor : UV/Vis Detektor
Lamda (λ) : 254 nm
Kolom : L7 (250 x 4.6 mm)
Laju Alir : 1.0 mL/menit
Volume Injeksi : 10 µL
Pelarut : Campuran Metanol – Air (70:30)
Fase Gerak : Campuran Methanol : Dapar Posfat pH 2.5 (80:20), Saring
dengan penyaring millipore ukuran 0,45 µm

Detector : UV/Vis Detector

Lamda (λ) : 254 nm
Column : L7 (250 x 4,6 mm)
Flow Rate : 1.0 mL/minutes
Injection Volume : 10 µL
Solvent : Mixture of Methanol – Water (70:30)
Mobile phase : Mixture of Methanol : Buffer Solution PH 2.5
(70:30), filtered with a 0,45 µm

Parameter Area Waktu Retensi Faktor Kapasitas Kolom Angka Lempeng Teoritis Faktor Ikutan
204923 8.391 40.95 6479 1.41
199050 8.386 40.93 6635 1.37
199264 8.38 40.9 6508 1.35
UKS
200002 8.366 40.83 6699 1.37
199843 8.308 40.54 6566 1.38
197618 8.276 40.38 6708 1.34
%SBR / Mean 1.25 0.57 40.76 6599 1.37
Kriteria Penerimaan ≤ 2% ≥ 2% ≥ 2000 ≤ 2%
MS/TMS MS

Tanggal :

Analis :
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 11 of 30

5.7.2 Selektivitas
Kromatogram larutan standar, zat aktif, spike placebo 100%, fasa gerak, placebo,
dan pelarut.
Sampel 1

Sampel 2
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 12 of 30

Sampel 3

Sampel 4
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 13 of 30

Sampel 5

Sampel 6
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 14 of 30

Sampel 7
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 15 of 30

5.7.3 Linearitas dan Rentang

Parameter Konsentrasi Teoritis (%) Luas Area Konsentrasi Analisis (%) Recovery (%) Regresi Linearitas
80 169536 78.18 97.73
90 196258 90.5 100.56
Linearitas 100 221577 102.17 102.17
110 238238 109.86 99.87
0.987
120 250162 115.35 96.13
Mean 99.29
SD 2.38
RSD 2.4
Kriteria Penerimaan Recovery / RSD (%) 80.00 - 110.00 / ≤ 11% ≥ 0.98
MS/TMS MS

Kurva Linearitas

Kurva Linearitas Natrii Diclofenac

270000
y = 203232x + 11922
250000 R² = 0.9747

230000

210000

190000

170000

150000
0.7 0.8 0.9 1 1.1 1.2 1.3

Kriteria Penerimaan

Linearitas / Linearity : r ≥ 0.98 Rentang / Range : Recovery : 80 % - 110%

RSD : ≤ 11%

Kesimpulan :
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 16 of 30

5.7.4 Batas Deteksi dan Uji Batas Kuantifikasi

Konsentrasi
Parameter Yi Y (Yi – Y)2
% ppm
80 0.8 169536 174507.6 24716806.56
90 0.9 196258 194830.8 2036899.84
100 1 221577 215154 41254929
110 1.1 238238 235477.2 7622016.64
LOD &
120 1.2 250162 255800.4 31791554.56
LOQ
y = 203232x + 11922 ∑ 107422206.6
a = 11922; b = 203232; r = 0.9873 SB 5983.93
LOD (ppm) 1.5058
LOD = 3×SB/b; LOQ = 10×SB/b
LOQ (ppm) 5.0192

Persamaan Linearitas : _______________________________________________________

Kesimpulan :

1. Akurasi
Uji akurasi sampel spiked placebo dengan konsentrasi 80%, 100%, dan 120%

Parameter Konsentrasi Teoritis (%) Konsentrasi Analisis (%) Luas Area Recovery (%)
82.31 174169 102.89
80 80.79 170949 100.99
80.44 170200 100.55
Mean 101.48
Akurasi
RSD 1.23
Rentang Recovery 100.55 - 102.89
Kriteria Penerimaan Recovery / RSD % 80.00 - 110.00 / ≤ 11%
MS / TMS MS
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 17 of 30

101.46 214690 101.46

100 104.96 222094 104.96
105.79 223846 105.79
Mean 104.07
RSD 2.21
Rentang Recovery 101.46 - 105.79
Kriteria Penerimaan Recovery / RSD % 80.00 - 110.00 / ≤ 11%
MS / TMS MS
122.28 258742 101.9
120 123.64 261604 103.03
122.73 259687 102.28
Mean 102.4
RSD 0.56
Rentang Recovery 101.90 - 103.03
Kriteria Penerimaan Recovery / RSD % 80.00 - 110.00 / ≤ 11%
MS / TMS MS

Contoh Perhitungan :
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 18 of 30

Kesimpulan :
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 19 of 30

2. Presisi
a. Uji Repitabilitas
Parameter Konsentrasi Teoritis Luas Area Konsentrasi Analisis
208205 96.01
219293 101.12
215482 99.36
100
219873 101.39
222108 102.42
Presisi 222178 102.45
Mean 100.46
SD 2.45
RSD (%) 2.44
Kapasitas Penerimaan RSD (%) ≤ 11%
MS / TMS MS
216674 99.91
211653 97.6
226790 104.58
100
208783 96.27
224534 103.54
Presisi
216457 99.81
Antara
Mean 100.29
SD 3.25
RSD (%) 3.24
Kapasitas Penerimaan RSD (%) ≤ 11%
MS / TMS MS

Contoh Perhitungan
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 20 of 30

Kriteria Penerimaan
\R
m Ripitabilitas : ≤ 11 %
Tyak
R

Kesimpulan

b. Presisi Antara
No Konsentrasi Target (%) Berat (mg) Luas Area Konsentrasi Analisis (%)
1 100
2 100
3 100
4 100
5 100
6 100
Mean
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 21 of 30

SD
RSD
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 22 of 30

Uji Fischer
Analis 1 Analis 2
Parameter Konsentrasi Luas Konsentrasi Konsentrasi Luas Konsentrasi
Teoritis (%) Area Analisis (%) Teoritis (%) Area Analisis (%)
208205 96.01 216674 99.91
219293 101.12 211653 97.6
215482 99.36 226790 104.58
100 100
219873 101.39 208783 96.27
222108 102.42 224534 103.54
222178 102.45 216457 99.81
Varian 1 (a) 6.02 Varian 2 (b) 13.12
Uji Fischer Mean 1 & 2 100.62
SD 1 & 2 3.17
RSD 1 & 2 3.15
F hit = (b)/(a) atau (a)/(b), Fhit > 1 2.18
F tab (n1-1, n2-1);(95%, 2 arah) 5.05
F hit ≤ tab (tidak ada perbedaan yang signifikan antara 2 pengujian)
Kriteria Penerimaan RSD(%) ≤ 11%
MS / TMS MS

Contoh Perhitungan
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 23 of 30

Kriteria Penerimaan
Repitabilitas
RSD : ≤ 11 %
Tidak ada perbedaan yang signifikan antara 2 pengujian

Kesimpulan

7. Ketegaran/ Robustness

Sampel (Luas Area)

Parameter Variasi Perlakuan Rata-rata
1 2 3 4 5 6
pH dapar FG 2.3 213240 213911 211630 209141 219910 212092 213321
pH dapar FG 2.7 205158 213697 211510 209166 210588 212031 210358
Flowrate 0.8 mL/menit 273045 269455 268513 265667 267333 269720 268955
Flowrate 1.2 mL/menit 178827 179912 182708 177869 179917 181706 180157
Robustness
Sampel 0 jam 207523 205990 209204 208799 207977 208169 207944
Sampel 2 jam 208522 209222 211744 206552 208526 207857 208737
Sampel 4 jam 209515 208494 213215 205450 208168 213230 209679
Sampel 6 jam 209607 212709 207619 204849 208983 209810 208929
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 24 of 30

Sampel 8 jam 211520 210308 207807 208245 210770 208726 209563

Sampel (Kadar (%))

Variasi Perlakuan Rata-rata RSD
1 2 3 4 5 6
pH dapar FG 2.3 98.34 98.65 97.6 96.45 101.42 97.81 98.38 1.7
pH dapar FG 2.7 96.38 100.39 99.36 98.26 98.93 99.61 98.82 1.41
Flowrate 0.8 mL/menit 107.11 105.7 105.33 104.21 104.86 105.8 105.5 0.93
Flowrate 1.2 mL/menit 103.76 104.39 106.01 103.2 104.39 105.43 104.53 0.99
Sampel 0 jam 98.71 97.98 99.51 99.32 98.93 99.02 98.91 0.54
Sampel 2 jam 99.71 100.04 101.25 98.77 99.71 99.39 99.81 0.83
Sampel 4 jam 99.73 99.25 101.5 97.8 99.09 101.5 99.81 1.46
Sampel 6 jam 99.77 101.25 98.83 97.51 99.48 99.87 99.45 1.25
Sampel 8 jam 100.69 100.11 98.92 99.13 100.33 99.36 99.76 0.72

Perhitungan

Kriteria Penerimaan

%RSD = ≤11 %

Kesimpulan
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 25 of 30

8. Rinse Recovery
Parameter Konsentrasi Teoritis (%) Konsentrasi Analisis (%) Luas Area Recovery (%)
87.66 172096 109.58
80 86.99 170790 108.74
86.46 169737 108.08
Mean 108.8
RSD 0.69
Rentang Recovery 108.08 - 109.58
Kriteria Penerimaan Recovery / RSD % 80.00 - 110.00 / ≤ 11%
MS / TMS MS
104.2 204576 104.2
100 102.64 201504 102.64
103.78 203758 103.78
Rinse
Mean 103.54
Recovery
RSD 0.78
Rentang Recovery 102.64 - 104.20
Kriteria Penerimaan Recovery / RSD % 80.00 - 110.00 / ≤ 11%
MS / TMS MS
118.21 232076 98.51
120 122.41 240335 102.01
118.06 231778 98.38
Mean 99.63
RSD 2.07
Rentang Recovery 98.38 - 102.01
Kriteria Penerimaan Recovery / RSD % 80.00 - 110.00 / ≤ 11%
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 26 of 30

MS / TMS MS

Perhitungan

Kriteria Penerimaan
% Recovery : 1. ≥ 80%
2. ≥ 50% lengkapi dengan alasan
Kesimpulan
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 27 of 30

9. Swab Recovery
Parameter Konsentrasi Teoritis (%) Konsentrasi Analisis (%) Luas Area Recovery (%)
81.17 159357 101.46
80 82.83 162621 103.54
80.98 158980 101.23
Mean 102.08
RSD 1.25
Rentang Recovery 101.23 - 103.54
Kriteria Penerimaan Recovery / RSD % 80.00 - 110.00 / ≤ 11%
MS / TMS MS
101.78 199831 101.78
100 93.23 183037 93.23
92.66 181921 92.66
Swab Mean 95.89
Recovery RSD 5.33
Rentang Recovery 92.66 - 101.78
Kriteria Penerimaan Recovery / RSD % 80.00 - 110.00 / ≤ 11%
MS / TMS MS
116.89 229484 97.41
120 116.69 229092 97.24
118.77 233172 98.98
Mean 97.88
RSD 0.98
Rentang Recovery 97.24 - 98.98
Kriteria Penerimaan Recovery / RSD % 80.00 - 110.00 / ≤ 11%
MS / TMS MS
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 28 of 30

Perhitungan

Kriteria Penerimaan
% Recovery : 1. ≥ 80%
2. ≥ 50% lengkapi dengan alasan

Kesimpulan
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 29 of 30

FORMULIR PENYIMPANGAN / DEVIATION FORM

Deviation Description : Initiate by:

No.

Criticality

□Critical Finding Date:

□Major

□Minor

Test # Corrective action description: Action by:

Approved by:

Target date:

Re-Inspection / Re-Test Results of corrective action Verified By:

Result: Checked by： Checked by： Closing Date:

Pass / Fail

Critical Deviation means deviation which will give impact to the performance of the system. This
deviation category may stop further testing to be conducted.
Major Deviation means deviation which may give impact to the performance of the system;
however other test in qualification stage may still be performed.
 RESIDUE ANALYTICAL METHOD VALIDATION
Product Name : Valid Date : .........................
Natrium Diklofenak 50 Mg
Protocol no. : MA-31-0002-00 Page 30 of 30

Minor Deviation means deviation which will not give impact to the performance of the system.
Example for this category is document which needs to be updated.
* Additional copy of this page can be duplicated as required