g., degradation by hydrolysis, photolysis, adhesion to glassware, etc.,

Smallest minimum weight according FI V and USP 3940 Smallest net weight w according USP: 38 2015; 392016 Sr = Sr = repeatability n = 10 = not more than 0. 10 W = Sr = repeatability n = 10 = not more than 0. 10 d = scale interval For analytical balance d = 0.1 or 0.01mg ; micro-balance 0.001 mg, w will be = 82 mg , 8.2 mg , 0.82 mg if SD = 0 or , 0.41 d Or w = 2000 SD USP 35FI V : Tolerance not exceed 0. 1 of the amount weight; so smallest weight must be 100.0 4 digitsand 10.00 mg 5 digits, or 1.000 mg 6 digits. Data below, usually are valid only for new balance Also USP 38 2015 and USP 39 2016 SelectivitySpecificity = the most important parameter SpecificitySelectivity USP, ICH, FDA: Specificity AOAC, IUPAC : Selectivity Specificity is the ability to determine the analyte unambiguously in the presence of other components, this includes degradation products, metabolites, matrix component etc. products, metabolites, matrix component etc. Selectivity means that the method provides responses for a number of chemical entities that may distinguished from each others. It means also the ability to separate the target analyte from all other components Selectivity evaluation for pharmaceutical preparations: Identity of API should be tested, and its selectivity should be proved. Please be careful if the identification method that described in Pharmacopeia Official method is not identical with its in Pharmacopeia Official method is not identical with its assay method e.g. Identification: IR, color reactions; assay : HPLC Why for some cases, identification of API in pharmaceutical preparations should be used by using 1 methods: IR, TLC, Color reactions “IR Library” should be validated routine A B C R DQC Lab. at Pharmaceutical Industry Nice if related compounds, possible degradation products, Densitograms λ λ λ λ = 260 nm obtained from: 1 solution of standard mometasone furoate, 2 extract from excipients of laboratory-made cream, 3 extract of laboratory-made cream, 4 solution of nipagin, 5 solution of nipasol, 6 extract of commercial ointment-1, 7 extract of commercial lotion, 8 extract of commercial cream-1, 9 extract of commercial ointment-2 and 10 extract of commercial cream-2. Peak identities: A mometasone furoate, B nipagin and nipasol, C unknown. Wulandari, L, Tan, KS., Indrayanto,G. 2003, J. Liq. Chromatogr. R T, 26, 109-117 A Standard products, known impurities can be tested The target peak must be proved regarding its identity and purity Peaks should be well separated F.Melianita, J. Witha, S.Arifin, WF.Karina, G. Indrayanto 2009. J. Liq. Chromatogr. R T, 32, 567-577 Rs should be not less 1.75 according USP Medicines Compendium, 2013 IF Impurities, related compounds, possible Degradation products were unavailable Cited from: D. Widiretani, I. Luailia, G. Indrayanto,

J. Planar Chromatogr. 262013 37-42

If we have no impurities andor degradation products; we should do stressed forced experiments to prove the selectivity. Identity and purity check of peaks A and B must be performed Cited from: D. Widiretani, I. Luailia, G. Indrayanto,

J. Planar Chromatogr. 262013 , 37-42

Determination of Xanthorrhizol in the rhizomes of Curcuma xanthorrhiza by GC FID Xanthorrhizol ?

F. Melinata G. Indrayanto 2006, Unpublished work

Should tried 3 different conditions For FID, RID, ELSD = Blind methods Purity Check using PDA detector HPLC or Densitometer TLC-Scanner Cited from: M. Yuwono G. Indrayanto, Profile Drugs Excipients and Related Methodology, Vol. 32, Elsevier, 2005. M.W. Dong, Modern HPLC for Practicing Scientist, Wiley, 2006 The purity of the peak can be calculated by comparing the MS of the u, a and d of the TIC peak. Acetylsalicylic acid 200 nm N=12804, Tf=1.20 Evaluation of the shape of acetylsalicylic acid Evaluation of the shape of acetylsalicylic acid chromatogram using 5 wavelengths chromatogram using 5 wavelengths 0 5 10 15min 200 nm 220 nm 240 nm 260 nm 280 nm N=12804, Tf=1.20 N=12970, Tf=1.20 N=12924, Tf=1.20 N=12887, Tf=1.20 N=12924, Tf=1.20 Analysis using LC MSMS triple Quad Cited from Agilent LCMSD triple Quad training, Singapore, May 2007 TA Sasaki, Chrom. Tech. JulyAugust 2008 Commission Decision 2002657EC Accoding to CD 2002657EC Off.J.Eur.Commun. 2002,L221,8 CD 2002657EC Off.J.Eur.Commun. 2002,L221,8 Mw: 868.04

M. Distl et al. 2009 Potato Research 52, 39-56 Mw:

852.07 The power of MRM MRM is nicer compare to SIR or SIM Why we need do the “ Why we need do the “identity test identity test” and “ ” and “ purity test purity test” of the peaks for ” of the peaks for each each samples for samples for quantitative analysis ? quantitative analysis ? •If the peak is not the target compound, the conclusion will be not correct. •If “impurity components” are included in the target peak, the quantitative-results in the target peak, the quantitative-results will be wrong •By Using LC-MSMS or GC-MSMS the target peak doesn’t need to be pure, it can contain 1 compounds which have same target ion; the Identity of the peaks can be differentiated by using MSMS spectrum but ratio of qualifier to quantifier ions should be in the acceptable range Linearity Calibration Linearity • The linearity of a method is its ability to provide measurement results that are directly proportional to the concentration of the analyte , or are directly proportional after mathematical transformation. • The linearity is usually documented as the ordinary least squares OLS curve, or simply as linear regression curve, of the measured responses peak area or height as a function of increasing analyte concentrations • Peak area shall be preferred compared to peak heights for making the calibration curve • The linearity of the detector can be obtained by diluting of the analyte stock solution, whilst the linearity of the analytical method can be determined by making a series of concentration of the analyte from independent preparations weighing, spiking

G. Indrayanto, Suciati, M. Yuwono 2010, in Encyclopedia Chromatography 3

rd Edition,Taylor Francis, pp.2336-2339