Farklı saklama şartlarında muhafaza edilen oksitetrasiklin, enrofloksasin, sülfonamid–trimetoprim ve levamizol içeren veteriner  müstahzarlarının orjinal ve açılmış şekillerindeki  
etkin madde düzeyi
Active matter levels in the original and open forms of the veterinary preparations kept under different storage conditions and containing oxytetracycline, enrofloxacin  
sulfonamid-trimetroprim and Levamisole
Yazar: SHAHRAM SAGHAEI
Danışman: PROF. DR. ENDER YARSAN
Ankara Üniversitesi / Sağlık Bilimleri Enstitüsü / Farmasötik Toksikoloji Ana Bilim Dalı
Derece: Doktora, 2014
Konu: Veteriner Hekimliği = Veterinary Medicine
Dizin: Antienfektif ajanlar = Anti infective agents ; Enrofloxacin = Enrofloxacin ; Levamizol = Levamisole ; Oksitetrasiklin = Oxytetracycline ; Sülfonamitler = Sulfonamides ; Trimetoprim = Trimethoprim ; İlaç depolama = Drug storage

Özet:
ÇalıĢmanın amacı, veteriner hekimlikte yaygın Ģekilde kullanılan antibakteriyel ilaçlardan oksitetrasiklin, enrofloksasin ve sülfametoksazol-trimetoprim ile antelmintik ilaçlardan levamizol'ün farklı saklama koĢullarında etken madde düzeylerinin değerlendirilmesidir. Bu kapsamda olacak Ģekilde açılmamıĢ haldeki orjinal ambalajlarında ve kapağı açılmıĢ Ģekildeki ilaçlar oda ısısında, karanlıkta ve buzdolabı ortamında farklı sürelerde bekletilerek etkin madde analizleri gerçekleĢtirildi.  Bu amaçla oksitetrasiklin içeren 2 müstahzar (50 mg/ml ve 200 mg/ml etkin madde), enrofloksasin içeren 1 müstahzar (100 mg/ml etkin madde), sülfametoksazol-trimetoprim içeren 1 müstahzar (200 mg/ml +40 mg/ml etkin madde) ve levamizol içeren 1 müstahzar (40 mg/ml etkin madde) incelendi. Her müstahzar için aynı seri numarasına sahip 5'er ilaç farklı saklama koĢullarında muhafaza edildi, baĢlangıçta, 1, 3, 6 ve 9. aylarda etkin madde miktarları analizleri yapıldı. Miktar analizleri HPLC ile gerçekleĢtirildi. Ayrıca ilaçların kullanılma süreleri dikkate alınarak; kapağı açılan ilaçlardan 24 ve 48. saatlerde de analizler yapıldı. Analizler sonucu elde edilen veriler rakamsal olarak (ppm ve grafikte etkin madde miktarıyla) değerlendirildi.  Oksitetrasiklin içeren (geleneksel) ve normal oda Ģartlarında muhafaza edilen A ve Yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (8.44±0.36, 5.73±0.25), (6.66±0.46, 7.17±0.27), (5.95±0.00, 7.16±0.31) ve (6.73±0.89, 7.30±0.50) ppm olarak elde edildi. Karanlıkta muhafaza edilen A ve yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (7.93±0.21, 4.66±0.21), (6.88±0.39, 6.99±0.48), (5.54±0.64, 7.04±0.26) ve (6.57±0.21, 6.39±0.98) ppm olarak; buzdolabı Ģartlarında muhafaza edilen A ve yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (7.85±0.14, 4.06±0.13), (8.65±0.21, 8.55±0.16), (5.62±0.08, 6.29±0.31) ve (6.70±0.55, 6.18±0.11) ppm olarak belirlendi. A ve B spesiyaliteleri analiz dönemlerinde olacak Ģekilde birbiriyle de karĢılaĢtırıldı. Buna göre normal oda Ģartlarında muhafaza edilen A ve B ilaçları için baĢlangıçta, 24.saat, 48.saat, 1., 3., 6., ve 9. aylarda gerçekleĢtirilen analizlerde etken madde düzeyleri sırasıyla (12.74±0.37, 11.09±0.79), (12.38±1.46, 11.97±0.29), (11.52±0.83, 11.04±0.51), (8.44±0.36, 7.59±0.33), (6.66±0.46, 7.70±0.21), (5.95±0.00, 4.92±0.24) ve (6.73±0.15, 6.72±0.08) ppm olarak tespit edildi. Karanlık Ģartlarında muhafaza edilenler için; sırasıyla (13.31±0.62, 12.83±0.36), (12.25±0.88, 11.73±0.69), (12.43±0.12, 10.90±1.83), (7.93±0.21, 7.81±0.23), (6.88±0.39, 6.99±0.14), (5.54±0.06, 6.68±0.40) ve (6.57±0.21, 5.69±1.11) ppm olarak; buzdolabı Ģartlarında muhafaza edilenler için de (11.15±0.71, 11.27±0.51), (13.76±0.39, 12.51±0.00), (11.57±0.88, 11.13±0.36), (7.85±0.14, 7.13±0.56), (8.65±0.21, 7.79±0.56), (5.62±0.08, 6.93±0.56) ve (6.70±0.55, 5.48±0.30) ppm olarak belirlendi.  Oksitetrasiklin uzun etkili içeren ve normal oda Ģartlarında muhafaza edilen A ve Yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (10.91±0.29, 11.38±0.99), (5.39±1.52, 8.31±0.51), (8.06±0.91, 7.69±0.43) ve (6.78±0.19, 7.99±0.42) ppm olarak elde edildi. Karanlıkta muhafaza edilen A ve yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (12.24±0.62, 10.76±0.58), (7.98±1.12, 8.65±0.10), (8.20±0.29, 7.81±0.43) ve (7.82±0.15, 6.79±0.95) ppm olarak; buzdolabı Ģartlarında muhafaza edilen A ve yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla  (13.32±1.27, 18.23±0.31), (8.20±0.57, 7.67±0.36), (8.27±0.25, 7.88±0.67) ve (7.92±0.21, 7.07±0.53) ppm olarak belirlendi. A ve B spesiyaliteleri analiz dönemlerinde olacak Ģekilde birbiriyle de karĢılaĢtırıldı. Buna göre normal oda Ģartlarında muhafaza edilen A ve B ilaçları için baĢlangıçta, 24.saat, 48.saat, 1., 3., 6., ve 9. aylarda gerçekleĢtirilen analizlerde etken madde düzeyleri sırasıyla (12.76±0.28, 13.53±0.43), (17.05±0.13, 12.43±0.91), (10.91±0.29, 
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10.96±0.54), (5.89±1.77, 8.42±0.26), (8.06±0.91, 9.03±0.21) ve (6.78±0.19, 6.79±0.22) ppm olarak tespit edildi.Karanlık Ģartlarında muhafaza edilenler için; sırasıyla (13.20±0.21, 15.09±0.93), (12.09±0.39, 13.39±0.12), (12.24±0.62, 13.83±0.51), (7.98±1.12, 8.12±0.60), (8.20±0.29, 8.74±0.29) ve (7.82±0.15, 7.15±0.22) ppm olarak; buzdolabı Ģartlarında muhafaza edilenler için de (12.42±0.22, 14.23±0.81), (14.29±0.57, 12.77±0.30), (13.32±1.27, 13.81±0.79), (8.20±0.57, 8.50±0.33), (8.27±0.25, 8.83±0.91) ve (7.92±0.21, 7.29±0.38) ppm olarak belirlendi. Enrofloksasin içeren ve normal oda Ģartlarında muhafaza edilen A ve Yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (10.33±0.63, 9.99±0.44), (9.02±0.84, 8.83±0.13), (7.96±1.26, 15.39±6.12) ve (6.72±0.95, 7.71±0.39) ppm olarak elde edildi. Karanlıkta muhafaza edilen A ve yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (10.04±0.11, 10.08±0.62), (8.97±0.74, 8.80±0.89), (7.15±0.29, 8.40±0.37) ve (7.57±0.35, 6.92±0.77) ppm olarak; buzdolabı Ģartlarında muhafaza edilenler için de (12.95±0.30, 11.05±0.58), (8.37±0.21, 8.07±0.17), (6.60±0.39, 7.10±1.71) ve (8.27±3.16, 9.29±3.28) ppm olarak belirlendi. A ve B spesiyaliteleri analiz dönemlerinde olacak Ģekilde birbiriyle de karĢılaĢtırıldı. Buna göre normal oda Ģartlarında muhafaza edilen A ve B ilaçları için baĢlangıçta, 24.saat, 48.saat, 1., 3., 6., ve 9. aylarda gerçekleĢtirilen analizlerde etken madde düzeyleri sırasıyla (5.19±0.79, 7.09±0.64), (6.42±0.50, 9.07±0.56), (6.01±0.16, 9.29±0.62), (10.33±0.63,18.83±0.24), (9.02±0.84, 15.01±0.92), (7.96±1.26, 13.34±0.31) ve (6.72±0.95, 12.67±0.24) ppm olarak tespit edildi. Karanlık Ģartlarında muhafaza edilenler için; sırasıyla (4.97±0.61, 6.39±0.91), (6.92±0.42, 8.73±0.38), (6.42±0.46, 9.70±0.38), (10.04±0.11, 15.64±0.56), (8.97±0.74, 12.63±1.23), (7.15±0.29, 11.31±0.79) ve (7.57±0.35, 11.32±0.89) ppm olarak; buzdolabı Ģartlarında muhafaza edilenler için de de (5.09±0.22, 3.86±0.23), (6.19±0.27, 7.97±0.28), (6.89±0.40, 9.25±0.11), (12.95±0.30, 15.08±0.79), (8.37±0.21, 15.28±0.79), (6.60±0.39, 11.56±0.78) ve (8.27±3.16, 13.39±1.12) ppm olarak belirlendi.  Levamizol içeren ve normal oda Ģartlarında muhafaza edilen A ve Yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (0.73±0.32, 1.69±0.59), (0.85±0.47, 1.36±0.36), (2.94±0.14, 4.70±0.44) ve (3.12±0.30, 2.17±1.11) ppm olarak elde edildi. Karanlıkta muhafaza edilen A ve yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (1.12±0.45, 0.98±0.39), (1.18±0.24, 1.46±0.03), (5.01±0.26, 3.54±1.02) ve (2.93±0.08, 2.49±0.29) ppm olarak; buzdolabı Ģartlarında muhafaza edilenler için de (1.03±0.48, 1.05±0.44), (0.93±0.54, 1.49±0.07), (5.08±0.28, 4.37±0.50) ve (2.13±1.18, 2.68±0.07) ppm olarak belirlendi. Sülfametoksazol içeren ve normal oda Ģartlarında muhafaza edilen A ve Yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (3.08±0.36, 2.22±0.10), (2.33±0.05, 2.33±0.08), (4.13±0.48, 4.30±0.22) ve (2.07±0.05, 2.15±0.11) ppm olarak tespit edildi. Karanlık Ģartlarında muhafaza edilenler için; sırasıyla (2.91±0.07, 2.34±0.01), (2.34±0.00, 2.55±0.20), (3.92±0.09, 4.31±0.10) ve (2.19±0.14, 2.19±0.01) ppm olarak; buzdolabı Ģartlarında muhafaza edilenler için de (3.24±0.29, 2.26±0.08), (2.61±0.24, 2.52±0.21), (4.36±0.39, 4.41±0.08) ve (2.03±0.06, 2.13±0.07) ppm olarak belirlendi. Trimetoprim içeren ve normal oda Ģartlarında muhafaza edilen A ve Yeni kapağı açılmıĢ ilaç için 1., 3., 6. ve 9. ayda elde edilen sonuçlar sırayla (1.97±0.14, 2.77±0.51), (3.04±0.48, 3.17±0.64), (1.84±0.09, 2.00±0.05) ve (3.34±0.95, 3.94±1.21) ppm olarak tespit edildi. Karanlık Ģartlarında muhafaza edilenler için; sırasıyla (2.08±0.10, 3.16±0.05), (3.53±0.42, 4.14±0.02), (1.91±0.04, 2.08±0.09) ve (4.28±0.44, 4.55±0.38) ppm olarak; buzdolabı Ģartlarında muhafaza edilenler için de (2.22±0.07, 2.94±0.14), (3.51±0.15, 3.67±0.17), (2.04±0.04, 2.07±0.05) ve (3.82±0.36, 4.35±0.06) ppm olarak belirlendi. ÇalıĢma sonuçları değerlendirildiğinde, ortak olarak spesiyalitelerdeki etkin madde miktarlarında zamana ve özellikle ısıya bağlı olarak azalmaların olduğu görülmüĢtür

Abstract:
The purpose of the study is to evaluate the active matter level of oxytetracycline, enrofloxacin and sulfamethoxazole-trimetroprim which are antibacterial drugs and levasimole which is an anthelmintic drug, which are used widely in veterinary medicine. Within this scope, the preparations in their original packages and in opened packages have been kept under room temperature, in the dark and in the refrigerator for different periods and they have been analyzed for active matters. For this purpose, 2 preparations containing oxytetracyline (50 mg/ml and 200 mg/ml of active matter), 1 preparation containing enrofloxacin (100 mg/ml of active matter), 1 preparation containing sulfamethoxazole- trimetroprim (200 mg/mL+40 mg/ml of active matter) and 1 preparation containing levamisole (40 mg/ml of active matter) have been examined. 5 each drugs with the same serial number for each preparation have been kept under different storage conditions. Initially, active matter quantities have been analyzed in the 1st, 3rd, 6th and 9th months. Quantities have been analyzed by means of HPLC. Besides, considering the life cycles of the drugs, those with open packages have been analyzed in the 24th and 48th hours as well. The data, obtained as a result of analysis have been evaluated quantitatively (ppm and active matter quantity in graphics).  The results obtained from a drug A containing oxytetracycline (traditional) and kept under normal room conditions and from a newly unwrapped drug in the 1st, 3rd, 6th and 9th months are given below respectively: (8.44 ± 0.36, 5.73 ± 0.25), (6.66 ± 0.46, 7.17 ± 0.27), (5.95 ±0.00, 7.16 ± 0.31) and (6.73 ± 0.89, 7.30 ± 0.50) ppm. The results oblained from a drug A, kept under the dark and from a newly unwrapped drug, in the 1st, 3rd, 6th and the 9th months are given below respetively: (7.93 ± 0.21, 4.66 ± 0.21), (6.88 ± 0.39, 6.99 ± 0.48), (5.54 ± 0.64, 7.04 ± 0.26) and (6.57 ± 0.21,6.39 ± 0.98) ppm. The results obtained from a drug A, kept in the refrigerator and from a newly unwrapped durg, in the 1st, 3rd, 6th and 9th months are given below respectively: (7.85 ± 0.14, 4.06 ± 0.13), (8.65 ± 0.21, 8.55 ± 0.16), (5.62 ± 0.08, 6.29 ± 0.31) and (6.70 ± 0.55, 6.18 ± 0.11) ppm The specialities of A and B have been compared during analysis periods. Thus, active matter levels obtained from the drugs A and B initially under normal room conditions in 24 hours, 48 hours, 1st, 3rd, 6th and 9th months are determined respectively as follows: (12.74 ± 0.37, 11.09 ± 0.79), (12.38 ± 1.46, 11.97 ± 0.29), (11.52 ± 0.83, 11.04 ± 0.51), (8.44 ± 0.36, 7.59 ± 0.33), (6.66 ± 0.46, 7.70 ± 0.21), (5.95 ± 0.00, 4.92 ± 0.24) and (6.73 ± 0.15, 6.72 ± 0.08) ppm. The results from the durgs kept under the dark are as follows respectively: (13.31 ± 0.62, 12.83 ± 0.36), (12.25 ± 0.88, 11.73 ± 0.69), (12.43 ± 0.12, 10.90 ± 1.83), (7.93 ± 0.21, 7.81 ± 0.23), (6.88 ± 0.39, 6.99 ± 0.14), (5.54 ± 0.06, 6.68 ± 0.40) and (6.57 ± 0.21, 5.69 ± 1.11) ppm. The results from the drugs kept in the refrigerator are as follows respectively: (11.15 ± 0.71, 11.27 ± 0.51), (13.76 ± 0.39, 1.51 ± 0.00), (11.51 ± 0.88, 11.13 ± 0.36), (7.85 ± 0.14, 7.13 ± 0.56), (8.65 ± 0.21, 7.79 ± 0.56), (5.62 ± 0.08, 6.93 ± 0.56) and (6.70 ± 0.55, 5.48 ± 0.30) ppm.  The results obtained from a drug A containing long acting oxytetracycline and kept under normal room conditions and from a newly unwrapped drug in the 1st, 3rd, 6th and 9th months are given below respectively: (10.91±0.29, 11.38±0.99), (5.39±1.52, 8.31±0.51), (8.06±0.91, 7.69±0.43) and (6.78±0.19, 7.99±0.42) ppm. The results oblained from a drug A, kept under the dark and from a newly unwrapped drug, in the 1st, 3rd, 6th and the 9th months are given below respetively: (12.24±0.62, 10.76±0.58), (7.98±1.12, 8.65±0.10), (8.20±0.29, 7.81±0.43) and (7.82±0.15, 6.79±0.95) ppm. The results obtained from a drug A, kept in the refrigerator and from a newly unwrapped durg, in the 1st, 3rd, 6th and 9th months are given below respectively: (13.32±1.27, 18.23±0.31), (8.20±0.57, 7.67±0.36), (8.27±0.25, 7.88±0.67) and (7.92±0.21, 7.07±0.53) ppm The specialities of A and B have been compared during analysis periods. Thus, active matter levels obtained from the drugs A and B initially under normal 
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room conditions in 24 hours, 48 hours, 1st, 3rd, 6th and 9th months are determined respectively as follows: (12.74±0.37, 11.09±0.79), (12.38±1.46, 11.97±0.29), (11.52±0.83, 11.04±0.51), (8.44±0.36, 7.59±0.33), (6.66±0.46, 7.70±0.21), (5.95±0.00, 4.92±0.24) and (6.73±0.15, 6.72±0.08) ppm. The results from the durgs kept under the dark are as follows respectively: (13.31±0.62, 12.83±0.36), (12.25±0.88, 11.73±0.69), (12.43±0.12, 10.90±1.83), (7.93±0.21, 7.81±0.23), (6.88±0.39, 6.99±0.14), (5.54±0.06, 6.68±0.40) and (6.57±0.21, 5.69±1.11) ppm. The results from the drugs kept in the refrigerator are as follows respectively: (11.15±0.71, 11.27±0.51), (13.76±0.39, 12.51±0.00), (11.57±0.88, 11.13±0.36), (7.85±0.14, 7.13±0.56), (8.65±0.21, 7.79±0.56), (5.62±0.08, 6.93±0.56) and (6.70±0.55, 5.48±0.30) ppm.  The results obtained from a drug A containing enrofloxacin and kept under normal room conditions and from a newly unwrapped drug in the 1st, 3rd, 6th and 9th months are given below respectively: (10.33±0.63, 9.99±0.44), (9.02±0.84, 8.83±0.13), (7.96±1.26, 15.39±6.12) and (6.72±0.95, 7.71±0.39) ppm. The results oblained from a drug A, kept under the dark and from a newly unwrapped drug, in the 1st, 3rd, 6th and the 9th months are given below respetively: (10.04±0.11, 10.08±0.62), (8.97±0.74, 8.80±0.89), (7.15±0.29, 8.40±0.37) and (7.57±0.35, 6.92±0.77) ppm. The results obtained from a drug A, kept in the refrigerator and from a newly unwrapped durg, in the 1st, 3rd, 6th and 9th months are given below respectively: (12.95±0.30, 11.05±0.58), (8.37±0.21, 8.07±0.17), (6.60±0.39, 7.10±1.71) and (8.27±3.16, 9.29±3.28) ppm The specialities of A and B have been compared during analysis periods. Thus, active matter levels obtained from the drugs A and B initially under normal room conditions in 24 hours, 48 hours, 1st, 3rd, 6th and 9th months are determined respectively as follows: (5.19±0.79, 7.09±0.64), (6.42±0.50, 9.07±0.56), (6.01±0.16, 9.29±0.62), (10.33±0.63,18.83±0.24), (9.02±0.84, 15.01±0.92), (7.96±1.26, 13.34±0.31) and (6.72±0.95, 12.67±0.24) ppm. The results from the durgs kept under the dark are as follows respectively: (4.97±0.61, 6.39±0.91), (6.92±0.42, 8.73±0.38), (6.42±0.46, 9.70±0.38), (10.04±0.11, 15.64±0.56), (8.97±0.74, 12.63±1.23), (7.15±0.29, 11.31±0.79) and (7.57±0.35, 11.32±0.89) ppm. The results from the drugs kept in the refrigerator are as follows respectively: (5.09±0.22, 3.86±0.23), (6.19±0.27, 7.97±0.28), (6.89±0.40, 9.25±0.11), (12.95±0.30, 15.08±0.79), (8.37±0.21, 15.28±0.79), (6.60±0.39, 11.56±0.78) and (8.27±3.16, 13.39±1.12) ppm.   The results obtained from a drug A containing levamisole and kept under normal room conditions and from a newly unwrapped drug in the 1st, 3rd, 6th and 9th months are given below respectively: (0.73±0.32, 1.69±0.59), (0.85±0.47, 1.36±0.36), (2.94±0.14, 4.70±0.44) and (3.12±0.30, 2.17±1.11) ppm. The results oblained from a drug A, kept under the dark and from a newly unwrapped drug, in the 1st, 3rd, 6th and the 9th months are given below respetively: (1.12±0.45, 0.98±0.39), (1.18±0.24, 1.46±0.03), (5.01±0.26, 3.54±1.02) and (2.93±0.08, 2.49±0.29) ppm. The results obtained from a drug A, kept in the refrigerator and from a newly unwrapped durg, in the 1st, 3rd, 6th and 9th months are given below respectively: (1.03±0.48, 1.05±0.44), (0.93±0.54, 1.49±0.07), (5.08±0.28, 4.37±0.50) and (2.13±1.18, 2.68±0.07) ppm.  The results obtained from a drug A containing sulfamethoxazole and kept under normal room conditions and from a newly unwrapped drug in the 1st, 3rd, 6th and 9th months are given below respectively: (3.08±0.36, 2.22±0.10), (2.33±0.05, 2.33±0.08), (4.13±0.48, 4.30±0.22) and (2.07±0.05, 2.15±0.11) ppm. The results oblained from a drug A, kept under the dark and from a newly unwrapped drug, in the 1st, 3rd, 6th and the 9th months are given below respetively: (2.91±0.07, 2.34±0.01), (2.34±0.00, 2.55±0.20), (3.92±0.09, 4.31±0.10) and (2.19±0.14, 2.19±0.01) ppm. The results obtained from a drug A, kept in the refrigerator and from a newly unwrapped durg, in the 1st, 3rd, 6th and 9th months are given below respectively: (3.24±0.29, 2.26±0.08), (2.61±0.24, 2.52±0.21), (4.36±0.39, 4.41±0.08) and (2.03±0.06, 2.13±0.07) ppm.  The results obtained from a drug A containing trimetroprim and kept under normal room conditions and from a newly unwrapped drug in the 1st, 3rd, 6th and 9th months are given below respectively: (1.97±0.14, 2.77±0.51), (3.04±0.48, 3.17±0.64), (1.84±0.09, 2.00±0.05) and (3.34±0.95, 3.94±1.21) ppm. The results oblained from a drug A, kept under the dark and from a newly unwrapped drug, in the 1st, 3rd, 6th and the 9th months are given below respetively: (2.08±0.10, 3.16±0.05), (3.53±0.42, 4.14±0.02), (1.91±0.04, 2.08±0.09) and 
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(4.28±0.44, 4.55±0.38) ppm. The results obtained from a drug A, kept in the refrigerator and from a newly unwrapped durg, in the 1st, 3rd, 6th and 9th months are given below respectively: (2.22±0.07, 2.94±0.14), (3.51±0.15, 3.67±0.17), (2.04±0.04, 2.07±0.05) and (3.82±0.36, 4.35±0.06) ppm.   
When the results from the study, it is seen that the quantities of active matters in the specialities commonly become less depending on time and especially ambient temperatures