Thesis (Ph.D)-Cairo University, 2023.

Bibliography: pages 147-157.

In this work, two different color-forming processes were used to study the
micro-determination of the antiviral drugs sofosbuvir (SOF) and daclatasvir
(DK) in their pure forms and in pharmaceutical preparations. The first colorforming process is an oxidation-reduction process using Ce(IV), followed by the
back determination of excess Ce(IV) using some chromotropic acid azo dyes or
titration against Fe(II) in the presence of ferrion indicator. The second colorforming process is ion associate, where SOF and DK were studied for their
ability to form ion associate with two Sulfonephthalein dyes (BCG and BPB).
DK has a high ability to form DK-BCG and DK-BPB with a suitable pH and
specific surfactant.
It comprises four chapters:
1. Chapter I: includes a short introduction about anti-viral drugs SOF and DK.
The reagents used in this work are C2B, Sulf (III), Arz (I) , Spd, ferrion, Fe (II),
BCG, and BPB.
2. Chapter II: includes a literature review of ways to measure SOF and DK, for
which not many articles, either spectrophotometric or chromatographic, have
been written. In this chapter, we also survey the methods used in the
determination of DK and SOF, as well as the use of Ce(IV) and sulfonephtalein
in pharmaceutical determination.
3. Chapter III: It talks about the experiments and describes the materials and
reagents used in the work, as well as their purity and where they came from.
This chapter also listed how to make solutions, what equipments to use, how to
do work, how to do calculations, and the math formulas that were used. There
are full explanations of how to make calibration graphs and how to find out how
different parameters affect their characteristics. The chapter also contains
methods for the evaluation of the sensitivity and quantification accuracy of the
cited drug in raw materials and pharmaceutical formulation.
4. Chapter IV: includes the results and discussion:
SUMMARY
145
In this chapter, we discuss in detail the proposed methods for determination of
the two antiviral drugs SOF and DK, where we have two color-forming
processes: oxidation-reduction and ion association.
First part
 Oxidation-reduction methods depended on oxidation of SOF and DK
using excess Ce(IV)
 The suitable temperature and time needed for complete reaction between
excess Ce(IV) and two drugs are 100oC for 25 minutes.
 Unreacted Ce(IV) was determined by two methods.
 The first method is a direct calibration curve using some chromotropic
acid azo dyes, such as C2B, Arz(I), Sulf(III), and Spd.
 Absorption spectra of the reagents C2B, Arz (I), Spd, and Sulf (III) were
found to have maximum absorption at 510, 505, 510, and 570 nm, respectively.
 The effect of chromotropic acid azo dye concentration suitable for the
determination SOF was 0.25 ml ×0.1 mmole for all the above chromotropic
acid azo dyes, while the most suitable volumes for DK were 2.2, 2.2, 2.5, and
1.6 mL from C2B, Arz (I), Sulf (III), and Spd, respectively.
 The sequence of addition was: Ce(IV)→drug(SOF or DK)→
chromotropic acid azodye→H2SO4
 The proposed methods have wide Beer’s law concentration ranges, high
molar absorptivity values and low values of Sandell's sensitivity indicating that
the proposed methods are of high sensitivity.
 Spectrophotometric titration for residual Ce(IV) using Fe(II) in the
presence of the ferrion indicator at 510 nm
 The structures of the oxidation products for SOF and DK with Ce(IV)
have been elucidated using FTIR, 1H-NMR and mass spectroscopy.
Second part
SUMMARY
146
 In the second process, we studied the ability of two the drugs (SOF and
DK) to form ion associations with some sulfonephthalein dyes (BCG and BPB);
it was found DK that had the ability to form ion associations with BCG and
BPB.
 Nonionic surfactants (Tween 80 and Triton 100) were able to prevent
turbidity and enhance the sensitivity of the method.
 DK-BCG and DK-BPB, the obtained green ion associates, absorbed
most of the incident light at 617 and 607 nm, respectively. the pH transition
ranges are 3.8–5.8 and 3.5–4.6 for BCG and BPB, respectively.
 The colored ion associates are stable over a wide temperature range (25–
40 °C).
 The stoichiometry of DK ions associated with both BCG and BPB was
found to be 1:2 (DK/dye).
 Large Beer's law concentration ranges, high molar absorptivity, and low
Sandell's sensitivity all point to high sensitivity in the proposed methods.
 The structure of the formed ion associates were studied, FTIR
absorption spectra of the ion-associates were compared to those of pure
sulfonephthalein and the medication. The FTIR spectral bands of the solid ionpairs changed, confirming their chemical interaction.

1H-NMR spectroscopy data was used to deduce the molecular structure
of the prepared ion-associate
 The deduced fragmentation patterns besides the molecular ion peaks
obtained from mass spectrometry ensure the formation of ion-pairs.

العمل الحالي هو محاولة لإيجاد طرق طيفية بسيطة لتحديد سريع ودقيق ودقيق ومنخفض التكلفة وحساس للأدوية المضادة للفيروسات سوفوسبوفير وداكلاتاسفير في أشكالها النقية وفي تركيباتها الصيدلانية.
عملية الأكسدة لتحديد سوفوسبوفير وداكلاتاسفير . يضاف كل دواء إلى تركيز ثابت السيريم الرباعي في وسط حمضي ، ويتم إجراء تفاعل الأكسدة والاختزال. يمكن تحديد الفائض السيريم الرباعي بطريقتين ، الطريقة الأولى هي التحليل الطيفي المباشر باستخدام أصباغ حمض الكروموتروبيك اسيد ازو داي. تم استخدام الكرمونروب 2 ب وارزنازوا 1 واسبادنس و سلفنازو الثلاثي لهذا الغرض طوال هذه الدراسة.
الطريقة الثانية هي طريقة المعايرة ، والتي تحدد فائض السيريم الرباعي بالمعايرة باستخدام الحديد الثنائي في وجود مؤشر الفريون.
تمت دراسة التركيب الناتج من الأكسدة الصلبة المفصوله للعقارين وتوضيحها باستخدام مطياف الأشعة تحت الحمراء ، والرنين المغناطيسي النووي البروتوني ، وقياس الطيف الكتلي.
الهدف الثاني هو دراسة قدرة سوفوسبوفير وداكلاتاسفير على تكوين روابط أيونية مع صبغين شائعين من سلفونيفثالين: البروموكريسول الأخضر وأزرق البروموفينول. تمت دراسة العوامل المختلفة التي تؤثر على التفاعل مثل الأس الهيدروجيني ونوع المخزن المؤقت والوقت ودرجة الحرارة والفاعل السطحي. سيتم عزل أيون مساعد في شكل صلب ويتم تمييزه باستخدام مطياف فورييه لتحويل الأشعة تحت الحمراء ، والرنين المغناطيسي النووي البروتوني (1H-NMR) ، وقياس الطيف الكتلي. تم تأكيد الهياكل المرتبطة الأيونية من خلال دراسة نظرية الكثافة الوظيفية

Issues also as CD.

Text in English and abstract in Arabic & English.